To what extent is alcohol consumption associated with breast cancer recurrence and second primary breast cancer?: A systematic review

Publication date: Available online 20 September 2016
Source:Cancer Treatment Reviews
Author(s): Phanthira Simapivapan, Anna Boltong, Allison Hodge
BackgroundThe association between alcohol intake and breast cancer recurrence or development of second primary breast cancer in the survivor population is unclear. The aim of this systematic review was to evaluate the existing evidence to assess the extent to which alcohol consumption is associated with breast cancer recurrence and second primary breast cancer.MethodsSix databases (Cochrane Library, EMBASE, MEDLINE, PubMed, Scopus and Web of Science) were searched using the following search phrase: (breast cancer OR breast adenocarcinoma OR breast neoplasm OR breast tumor) AND (alcohol^∗ OR alcohol intake OR alcohol consumption OR ethanol) AND (recurrence OR second primary). A narrative synthesis was conducted on studies meeting the inclusion criteria.ResultsAfter screening, 16 studies met the inclusion criteria, of which 11 assessed breast cancer recurrence and 5 assessed second primary breast cancer. Considerable clinical and methodological heterogeneity was observed between studies. Approximately half of the included studies observed a modest, but significant, association between alcohol consumption and increased risk of breast cancer recurrence or development of a second primary breast cancer, with some studies observing associations from as little as six grams of alcohol intake per day. Two studies suggest this association was stronger in postmenopausal women.ConclusionThere is some evidence that alcohol consumption increases the risk of breast cancer recurrence, particularly in postmenopausal women. The association between alcohol and development of a second primary breast cancer is less clear. Inconsistencies in methodology and results across studies complicate attempts to develop a cohesive interpretation of findings.



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Mechanism of drug resistance in relation to site of metastasis: Meta-analyses of randomized controlled trials in advanced breast cancer according to anticancer strategy

Publication date: Available online 20 September 2016
Source:Cancer Treatment Reviews
Author(s): Saroj Niraula, Alberto Ocana
BackgroundBreast cancer is heterogeneous at different levels: biologic subtypes, intratumoral areas, and sites of metastases. Randomized controlled trials (RCTs) classify metastatic sites as visceral or non-visceral, but this has little influence in treatment decisions, particularly in the absence of clinical urgency. Indeed, it is unclear if response to treatments differs among sites of metastases.Patients and MethodsRCTs investigating 3 different anticancer strategies in metastatic breast cancer were identified: (1) new hormonal therapy, (2) new targeted therapies in hormone receptor positive tumours (everolimus or palbociclib), and (3) new anti-HER2 therapies. RCTs reporting hazard ratios (HR) for Progression Free Survival (PFS) and Overall Survival (OS) for sub-groups based on sites of metastases were weighted using generic inverse variance approach, and pooled in meta-analyses using Revman 5.3. Subgroup difference was tested with Chi² statistics.ResultsEleven RCTs (6,701 pts.) qualified. There was a significant difference in PFS between women with visceral versus non-visceral metastases when two endocrine strategies were compared, with benefits limited to women with visceral metastases [Pooled HR 0.85; 95% CI, 0.77-0.95 versus 1.02(0.88-1.18) for non-visceral; p(difference)=0.05]. However, combination of an endocrine therapy and a targeted therapy was associated with better PFS compared to endocrine therapy alone for both groups [HR 0.51(0.43-0.60) versus 0.45(0.36-0.56) for non-visceral; p(difference)=0. 36]. Novel HER-2 targeted therapies were associated with significantly better PFS and OS only in visceral metastases [HR 0.59 (0.52-0.66) versus 0.71(0.44-1.13) for non-visceral, p(difference)=0.45, for PFS; and 0.64 (0.56-0.73) versus 0.82 (0.57=1.19) for non-visceral, p(difference)=0.20, for OS].ConclusionCombination of targeted agents and endocrine therapy results in concordant, superior PFS suggesting targetable endocrine resistance across metastatic sites. Discordant responses with endocrine strategy alone support use of targeted therapy, rather than change in endocrine agent at disease progression. HER2 targeted therapies may be less effective in areas of poor vascularization.



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The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Publication date: December 2016
Source:Neurobiology of Aging, Volume 48
Author(s): Claire Lancaster, Naji Tabet, Jennifer Rusted
Possession of an Apolipoprotein E (APOE) e4 allele is an established risk factor for Alzheimer's disease, whereas the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. Sixty-six volunteers, aged 45–55 years, completed 3 tasks that provided complementary measures of attentional control: prospective memory, sustained attention, and inhibition. Performance was compared between e2 carriers, e4 carriers, and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared with the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes.



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Varied incidence of immediate adverse reactions to low-osmolar non-ionic iodide radiocontrast media used in computed tomography

Abstract

Background

Low-osmolar nonionic radiocontrast media (RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions (ADRs) to various low-osmolar nonionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low-osmolar nonionic RCMs used in computed tomography (CT).

Methods

Severance Hospital has collected data for adverse reactions occurring in-hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286,087 RCM-contrasted CT examinations of 142,099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analyzed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day.

Results

Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%).

Conclusions

The incidence of immediate ADRs varied according to the low-osmolar nonionic RCM used. Iopromide-induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations.

This article is protected by copyright. All rights reserved.

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Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodeling in asthma

Abstract

Background

Allergic asthma is characterized by inflammation and airway remodeling. Airway remodeling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in airway smooth muscle remodeling remains unknown.

Objective

To investigate the role of calpain in asthmatic airway remodeling as well as the underling mechanism.

Methods

The mouse asthma model was made by ovalbumin sensitization and challenge. Calpain conditional knockout mice were studied in the model. Airway smooth muscle cells (ASMCs) were isolated from smooth muscle bundles in airway of rats. Cytokines IL-4, IL-5, TNF-α and TGF-β1, and serum from asthmatic patients were selected to treated ASMCs. Collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs were analyzed.

Results

Inhibition of calpain using calpain knockout mice attenuated airway smooth muscle remodeling in mouse asthma models. Cytokines IL-4, IL-5, TNF-α and TGF-β1, and serum from asthmatic patients increased collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs, which were blocked by the calpain inhibitor MDL28170. Moreover, MDL28170 reduced cytokine-induced increases in Rictor protein which is the most important component of mammalian target of rapamycin complex 2 (mTORC2). Blockage of the mTORC2 signal pathway prevented cytokine-induced phosphorylation of Akt, collagen-I synthesis and cell proliferation of ASMCs, and attenuated airway smooth muscle remodeling in mouse asthma models.

Conclusions

Our results indicate that calpain mediates cytokine-induced collagen-I synthesis and proliferation of ASMCs via the mTORC2/Akt signaling pathway, thereby regulating airway smooth muscle remodeling in asthma.

This article is protected by copyright. All rights reserved.

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In silico, in vitro and case-control analyses as an effective combination for analyzing BRCA1 and BRCA2 unclassified variants in a population-based sample

Publication date: Available online 20 September 2016
Source:Cancer Genetics
Author(s): Marta Rodríguez-Balada, Bàrbara Roig, Lourdes Martorell, Mireia Melé, Mònica Salvat, Elisabet Vilella, Joan Borràs, Josep Gumà
Ascertaining the clinical consequences of BRCA1 and BRCA2 variants of uncertain significance (VUS) is currently indispensable for providing effective genetic counseling and preventive actions for families with hereditary breast and ovarian cancer (HBOC). To this end, we conducted a combination of in silico prediction and cDNA splicing analyses of 13 BRCA1 and 10 BRCA2 VUS identified in our cohort as well as a case-control analysis in a population-based sample of 10 recurrent VUS. We observed consistent results between the in silico predictions and sequencing analyses for all analyzed VUS. An abnormal cDNA pattern was observed for variants c.212+1G>A and c.5278-1G>A in BRCA1 and c.516+2T>A and c.8168A>G in BRCA2 according to in silico splicing prediction.. A case-control study of VUS confirmed the polymorphisms of the c.67+62A>G, c.7008-62A>G and c.8851G>A BRCA2 variants previously published. c.4068G>A in the BRCA2 gene can also be considered a polymorphism due to its occurrence at a frequency greater than 1% in our population.Our study shows that employing population-based analysis and a combination of several in silico methods yields highly accurate information, resulting in a reliable tool for selecting variants for cDNA sequencing analysis in routine cancer genetic counseling units.



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Novel Insights into PML-Dependent Oncosuppression

Publication date: Available online 20 September 2016
Source:Trends in Cell Biology
Author(s): Lorenzo Galluzzi
At odds with its nuclear counterpart, extranuclear promyelocytic leukemia constitutively inhibits autophagy, hence limiting cancer progression. These data raise the interesting possibility that some tumor suppressors have become specialized to operate at multiple subcellular compartments for counteracting different aspects of the oncogenic process.



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N-cadherin regulates beta-catenin signal and its misexpression perturbs commissural axon projection in the developing chicken spinal cord

Abstract

N-cadherin is a calcium-sensitive cell adhesion molecule that plays an important role in the formation of the neural circuit and the development of the nervous system. In the present study, we investigated the function of N-cadherin in cell–cell connection in vitro with HEK293T cells, and in commissural axon projections in the developing chicken spinal cord using in ovo electroporation. Cell–cell connections increased with N-cadherin overexpression in HEK293T cells, while cell contacts disappeared after co-transfection with an N-cadherin-shRNA plasmid. The knockdown of N-cadherin caused the accumulation of β-catenin in the nucleus, supporting the notion that N-cadherin regulates β-catenin signaling in vitro. Furthermore, N-cadherin misexpression perturbed commissural axon projections in the spinal cord. The overexpression of N-cadherin reduced the number of axons that projected alongside the contralateral margin of the floor plate, and formed intermediate longitudinal commissural axons. In contrast, the knockdown of N-cadherin perturbed commissural axon projections significantly, affecting the projections alongside the contralateral margin of the floor plate, but did not affect intermediate longitudinal commissural axons. Taken together, these findings suggest that N-cadherin regulates commissural axon projections in the developing chicken spinal cord.

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Receding Gums: Treatment Options and Causes

Gingival recession is when the gum tissue covering the root of the tooth is pushed back. Learn about its causes and forms of treatment with this article.

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Human tolerogenic dendritic cells generated with protein kinase C inhibitor are optimal for functional regulatory T cell induction – A comparative study

Publication date: Available online 19 September 2016
Source:Clinical Immunology
Author(s): Endy Adnan, Takuya Matsumoto, Jun Ishizaki, Sachiko Onishi, Koichiro Suemori, Masaki Yasukawa, Hitoshi Hasegawa
Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF)-β, and a combination of peroxisome proliferator-activated receptor γ agonist and retinoic acid. All tDCs had a semi-mature DC phenotype. PKCI-, TGF-β-, and Rapa-tDCs showed CCR7 expression and migration to CCL19, but other tDCs showed little or none. PKCI- and IL-10-tDCs induced functional regulatory T cells more strongly than other tDCs. The tolerogenic properties of all tDCs were stable against proinflammatory stimuli. Furthermore, PKCI-tDCs were generated from patients with rheumatoid arthritis and primary Sjögren's syndrome. Therefore, PKCI-tDCs showed the characteristics best suited for tolerance-inducing therapy.



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Long-term Outcomes of Superficial Esophageal Squamous Cell Carcinoma

Condition:   Esophageal Neoplasms
Intervention:  
Sponsors:   Shanghai Zhongshan Hospital;   The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School;   Tongji Hospital;   The affiliated Hospital of Shihezi University
Not yet recruiting - verified September 2016

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Endostar Combined With Concurrent Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Carcinoma
Interventions:   Drug: Endostar;   Drug: DDP
Sponsor:   First Affiliated Hospital of Guangxi Medical University
Not yet recruiting - verified September 2016

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Ontario-wide Cancer TArgeted Nucleic Acid Evaluation

Conditions:   Breast Cancer;   Lung Cancer;   Colorectal Cancer;   Melanoma;   Gynecological Cancer;   Genitourinary Cancer;   Pancreatobiliary Cancer;   Gastrointestinal Cancer;   Head and Neck Cancer;   Rare Cancer;   Unknown Primary Cancer
Intervention:  
Sponsors:   University Health Network, Toronto;   Princess Margaret Hospital, Canada
Recruiting - verified September 2016

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Potentiation of Cisplatin-based Chemotherapy by Digoxin in Advanced Unresectable Head and Neck Cancer Patients

Condition:   Head and Neck Cancer
Intervention:   Drug: Digoxin
Sponsors:   Assistance Publique - Hôpitaux de Paris;   Cancer Research and Personalized Medicine (Carpem);   Laboratoire d'excellence en immuno-oncologie (Labex)
Not yet recruiting - verified June 2016

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Synthesis and Structure–Activity Relationships of 1-Benzylindane Derivatives as Selective Agonists for Estrogen Receptor Beta

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Shigeru Yonekubo, Nobuhiko Fushimi, Takashi Miyagi, Osamu Nakanishi, Kenji Katsuno, Motoyasu Ozawa, Chiaki Handa, Noritaka Furuya, Hideyuki Muranaka
The estrogen receptor beta (ERβ) selective agonist is considered a promising candidate for the treatment of estrogen deficiency symptoms in ERβ-expressing tissues, without the risk of breast cancer, and multiple classes of compounds have been reported as ERβ selective agonists. Among them, 6-6 bicyclic ring-containing structures (e.g., isoflavone phytoestrogens) are regarded as one of the cyclized analogues of isobutestrol 5b, and suggest that other cyclized scaffolds comprising 5-6 bicyclic rings could also act as selective ERβ ligands.In this study, we evaluated the selective ERβ agonistic activity of 1-(4-hydroxybenzyl)indan-5-ol 7a and studied structure–activity relationship (SAR) of its derivatives. Some functional groups improved the properties of 7a; introduction of a nitrile group on the indane-1-position resulted in higher selectivity for ERβ (12a), and further substitution with a fluoro or a methyl group to the pendant phenyl ring was also preferable (12b, d, and e). Subsequent chiral resolution of 12a identified that R-12a has a superior profile over S-12a. This is comparable to diarylpropionitrile (DPN) 5c, one of the promising selective ERβ agonists and indicates that this indane-based scaffold has the potential to provide better ERβ agonistic probes.

Graphical abstract

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Synthesis and antimicrobial activity of small cationic amphipathic aminobenzamide marine natural product mimics and evaluation of relevance against clinical isolates including ESBL-CARBA multi-resistant bacteria

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Elizaveta M. Igumnova, Ekaterina Mishchenko, Tor Haug, Hans-Matti Blencke, Johanna U. Ericson Sollid, Elizabeth G. Aarag Fredheim, Silje Lauksund, Klara Stensvåg, Morten B. Strøm
A library of small aminobenzamide derivatives was synthesised to explore a cationic amphipathic motif found in marine natural antimicrobials. The most potent compound E23 displayed minimal inhibitory concentrations (MICs) of 0.5 – 2 μg/ml against several Gram-positive bacterial strains, including methicillin resistant Staphylococcus epidermidis (MRSE).E23 was also potent against 275 clinical isolates including Staphylococcus aureus, Enterococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci (VRE), and ESBL-CARBA multi-resistant Gram-negative bacteria. The study demonstrates how structural motifs found in marine natural antimicrobials can be a valuable source for making novel antimicrobial lead-compounds.

Graphical abstract

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Tyrosyl-DNA phosphodiesterase inhibitors: Progress and potential

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Sergey S. Laev, Nariman F. Salakhutdinov, Olga I. Lavrik
DNA topoisomerases are essential during transcription and replication. The therapeutic mechanism of action of topoisomerase inhibitors is enzyme poisoning rather than catalytic inhibition. Tyrosyl-DNA phosphodiesterases 1 or 2 were found as DNA repair enzymes hydrolyzing the covalent bond between the tyrosyl residue of topoisomerases I or II and the 3'- or 5'-phosphate groups in DNA, respectively. Tyrosyl-DNA phosphodiesterase 1 is a key enzyme in DNA repair machinery and a promising target for antitumor and neurodegenerative therapy. Inhibitors of tyrosyl-DNA phosphodiesterase 1 could act synergistically with topoisomerase I inhibitors and thereby potentiate the effects of topoisomerase I poisons. Tyrosyl-DNA phosphodiesterase 2 is an enzyme that specifically repairs DNA damages induced by topoisomerase II poisons and causes resistance to these drugs. Selective inhibition of tyrosyl-DNA phosphodiesterase 2 may be a novel approach to overcome intrinsic or acquired resistance to topoisomerase II-targeted drug therapy. Thus, agents that inhibit tyrosyl-DNA phosphodiesterases 1 and 2 have many applications in biochemical and physiological research and they have the potential to become anticancer and antiviral drugs. The structures, mechanism of action and therapeutic rationale of tyrosyl-DNA phosphodiesterase inhibitors and their development for combinations with topoisomerase inhibitors and DNA damaging agents are discussed.

Graphical abstract

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A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities

Publication date: Available online 19 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Chelliah Bharkavi, Sundaravel Vivek Kumar, Mohamed Ashraf Ali, Hasnah Osman, Shanmugam Muthusubramanian, Subbu Perumal
A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07 μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 < 1.56 μM) and 6l (IC50 = 2.87 μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16 μmol/L respectively.

Graphical abstract

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Response of wine grape growth, development and the transfer of copper, lead, and cadmium in soil-fruit system to sludge compost amendment

Abstract

Sludge is an organic waste after domestic sewage being treated and contains phytonutrients and organic matter. In this study, recycling of sludge compost (SC) and its compound fertilizer (SCF) to wine grape resulted in improvement in vegetative growth, reproductive development of wine grape, and potential wine quality of grape fruit. The amounts of Cu, Pb, and Cd in grape fruit were significantly higher in response to sludge amendment than in the control, but were all below the permissible limits for agricultural product. The contents of Cu and Pb in sludge-amended soil decreased with increasing soil depth, but Cd content increased with soil depth. Ongoing monitoring of on mobility of Cd downward is proposed with sludge recycling to wine grape soil.

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A modified biotrickling filter for nitrification-denitrification in the treatment of an ammonia-contaminated air stream

Abstract

A conventional biotrickling filter for airborne ammonia nitrification has been modified, by converting the liquid sump into a biological denitrifying reactor. The biotrickling filter achieves an average ammonia removal efficiency of 92.4 %, with an empty bed retention time (EBRT) equal to 36 s and an average ammonia concentration of 54.7 mg Nm⁻³ in the raw air stream. The denitrification reactor converts ammonia into inert gas N₂, in addition to other important advantages connected to the alkaline character of the biochemical pathway of the denitrifying bacteria. Firstly, the trickling water crossing the denitrification reactor underwent a notable pH increase from 7.3 to 8.0 which prevented the acidic inhibition of the nitrifying bacteria due to the buildup of nitric and nitrous acids. Secondly, the pH increase created the ideal conditions for the autotrophic nitrifying bacteria. The tests proved that an ammonia removal efficiency of above 90 % can be achieved with an EBRT greater than 30 s and a volumetric load lower than 200 g NH₃ m⁻³ day⁻¹. The results of the biofilm observation by using a scanning confocal laser microscope are reported together with the identification of degrading bacteria genera in the biotrickling filter. The efficiency of the plant and its excellent operational stability highlight the effectiveness of the synergistic action between the denitrification reactor and the biotrickling filter in removing airborne ammonia.

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Effects of salinity on simultaneous reduction of perchlorate and nitrate in a methane-based membrane biofilm reactor

Abstract

This study builds upon prior work showing that methane (CH₄) could be utilized as the sole electron donor and carbon source in a membrane biofilm reactor (MBfR) for complete perchlorate (ClO₄⁻) and nitrate (NO₃⁻) removal. Here, we further investigated the effects of salinity on the simultaneous removal of the two contaminants in the reactor. By testing ClO₄⁻ and NO₃⁻ at different salinities, we found that the reactor performance was very sensitive to salinity. While 0.2 % salinity did not significantly affect the hydrogen-based MBfR for ClO₄⁻ and NO₃⁻ removals, 1 % salinity completely inhibited ClO₄⁻ reduction and significantly lowered NO₃⁻ reduction in the CH₄-based MBfR. In salinity-free conditions, NO₃⁻ and ClO₄⁻ removal fluxes were 0.171 g N/m²-day and 0.091 g/m²-day, respectively, but NO₃⁻ removal fluxes dropped to 0.0085 g N/m²-day and ClO₄⁻ reduction was completely inhibited when the medium changed to 1 % salinity. Scanning electron microscopy (SEM) showed that the salinity dramatically changed the microbial morphology, which led to the development of wire-like cell structures. Quantitative real-time PCR (qPCR) indicated that the total number of microorganisms and abundances of functional genes significantly declined in the presence of NaCl. The relative abundances of Methylomonas (methanogens) decreased from 31.3 to 5.9 % and Denitratisoma (denitrifiers) decreased from 10.6 to 4.4 % when 1 % salinity was introduced.

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Theoretical and experimental study of the mechanisms of phosphate removal in the system containing Fe(III)-ions

Abstract

A process-oriented investigation of phosphate removal by ferric salt was carried out in this study. The kinetics of amorphous ferric phosphate (FePO₄(s)) formation has been investigated over the pH range of 6.0–8.0 using sulfosalicylic acid as a competitive ligand. The FePO₄(s) formation rate constants varied in a narrow range over the pH range examined in this study. And the maximum of (0.90 ± 0.11) × 10⁴ L mol⁻¹ s⁻¹ was obtained at pH 7.5 and the minimum value of (0.05 ± 0.01) × 10⁴ L mol⁻¹ s⁻¹ was obtained at pH 6.0. These values are two orders of magnitude lower than the rate constants for Fe(III) hydrolysis-precipitation, and hence, the extent of FePO₄(s) formation when ferric ions are added to aqueous solution is extremely low. Subsequently, the characteristics of the amorphous ferric oxide (AFO) with different ages were investigated, and it was found that the BET surface area, the average pore width, and the charge capacitance were various for different AFO with various ages. Phosphate adsorption by AFO was significantly affected by AFO aging and the manner of adding Fe(III), which was successfully described by a diffuse layer model. By using surface sites concentration obtained, the kinetics constant of AFO aging could be calculated by a functional equation at a certain pH and time.

Graphic abstract

Description of the precipitation and aging processes for the phosphate removal by Fe(III)-ions

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Phosphorus partitioning in sediments from a tropical reservoir during a strong period of drought

Abstract

Monitoring phosphorus (P) concentration in water and sediments in the Castanhão reservoir, under intensive aquaculture, in Northeastern Brazil showed internal process to dominate P cycling following a reduction of reservoir volume due to an extended drought period. A strong negative correlation between soluble reactive phosphorus in surface waters (SRPs) with the reservoir volume results from diminishing dilution capacity; bottom water SRP showed no significant correlation with volume and imply SRP remobilization to surface layers. Total suspended solids (TSS) showed a significant correlation with chlorophyll-a, suggesting change primary productivity following SRP enrichment of surface waters and living cells dominating the TSS. As a result, eutrophication, as established by a trophic state index, was triggered in the reservoir probably enforced by intensive fish farming effluents, whose nutrients accumulated in bottom waters and which became available due to breaking of the thermocline. Since low rainfall periods are typical of the semiarid region and tend to be more frequent and stronger due to climate change, multiple use of reservoirs in NE Brazil should be reevaluated.

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Flexible Fiber Optic Carbon-Dioxide Laser Assisted Stapedotomy in Otosclerosis

Objective. The aim of this study is to analyze the hearing and vestibular outcome of patients with otosclerosis who have been operated on by fiber optic flexible CO2 laser. Study Design. A preliminary and retrospective study was conducted in 30 patients with otosclerosis. Results. Comparative analysis of average air conduction thresholds ( dB versus  dB) and air-bone gaps ( dB versus  dB) before and after the surgery were statistically significant (

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Immunosuppressive effect of ASP2408, a novel CD86-selective variant of CTLA4-Ig, in rats and cynomolgus monkeys

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Shinsuke Oshima, Yasutomo Fujii, Erik E. Karrer, Fujiko Takamura, Steven J. Chapin, Margaret Neighbors, Sridhar Viswanathan, Bruce H. Devens, Yasuyuki Higashi, Hidekazu Mizuhara
The CTLA4-Ig fusion proteins abatacept and belatacept inhibit CD28-mediated T cell activation by binding CD80 (B7-1) and CD86 (B7-2) costimulatory ligands and are clinically proven immunosuppressants used for rheumatoid arthritis and renal transplantation, respectively. Abatacept and belatacept preferentially bind CD80, yet CD86 has been implicated as the dominant ligand for CD28-mediated costimulation of T cells. We investigated the immunosuppressive effects of ASP2408, a novel CTLA4-Ig with CD86 selectivity and high potency created by directed evolution methods. Here we evaluated the effect of ASP2408 in vitro using cynomolgus monkey and rat T cell proliferation assays and in vivo using cynomolgus monkey tetanus toxoid (TTx) immunization and a rat rheumatoid arthritis model. ASP2408 was 290-fold and 21-fold more potent in suppressing in vitro monkey T cell proliferation than abatacept and belatacept, respectively. ASP2408 inhibited anti-TTx immunological reactions in cynomolgus monkey at a 10-fold lower dose level than belatacept, through complete CD86 and partial CD80 receptor occupancies, and also suppressed inflammation in the rat collagen-induced arthritis model. Overall, improved immunosuppressive potency of ASP2408 relative to abatacept and belatacept correlated well with improved CD86 binding affinity. These results may support the advantage of preferential enhancement of CD86 binding affinity to inhibit T cell-mediated immune response and improved dosing convenience in humans relative to abatacept or belatacept.



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CONDYDAV : étude observationnelle multicentrique des patients présentant des condylomes dans les dispensaires antivénériens en France

Publication date: Available online 19 September 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J. Chanal, S. Fouéré, F. Yassir-Oria, N. Spenatto, F. Bouscarat, E. Picot, P. Martinet, C. Vernay-Vaisse, F. Pelletier, C. Courtieu, V. Baclet, C. Bernier, D. Aymar-Moulene, F. Dupuis-Fourdan, A. Passeron, C. Bara-Passot, A.-L. Pinault, L. Misery, M. Janier, N. Dupin
IntroductionLes condylomes sont un des premiers motifs de consultation dans les centres de maladies sexuellement transmissibles (MST). Depuis 2007, la vaccination contre les papillomavirus humains (PVH) est autorisée en France. L'objectif de notre étude était de déterminer la prévalence des condylomes et le profil clinique et épidémiologique des patients avec condylomes consultant dans des centres de MST.Patients et méthodesÉtude observationnelle prospective multicentrique, non interventionnelle, analysant les données épidémiologiques et cliniques des patients porteurs de condylomes ainsi que les traitements utilisés dans 15 centres de MST entre le 1^er janvier et le 31 mars 2012.RésultatsOnt été inclus 372 hommes et 111 femmes ; l'âge moyen était de 31,2ans. Les femmes étaient plus jeunes que les hommes (respectivement 28,9 et 31,7ans, p<0,05). Quatre cent quatorze patients étaient hétérosexuels et 66 étaient des hommes ayant des rapports sexuels avec des hommes (HSH). Chez les hommes, 230 avaient une atteinte du pénis isolée et 46 une atteinte de l'anus isolée. En tout, 76 avaient une atteinte de l'anus, dont 26 étaient HSH. Chez les femmes, 76 avaient une atteinte de la vulve isolée et 22 une co-infection de la vulve et de l'anus. L'atteinte anale était significativement plus fréquente chez les HSH et les femmes que chez les hommes hétérosexuels (p<0,0001 et p=0,004, respectivement). Trois femmes avaient été vaccinées : deux par Gardasil^® et une par Cervarix^®. Le traitement de première intention était la cryothérapie dans les deux groupes.ConclusionUn examen complet, notamment anal, doit être effectué chez les femmes et chez les HSH. Une globalisation de la vaccination anti-HPV devrait permettre une réduction des infections et l'implantation d'une stratégie globale de contrôle de la maladie.BackgroundSince 2007 in France, human papilloma virus (HPV) vaccination has been licensed for use as a vaccine against HPV 6, 11, 16 and 18. The impact on the epidemiology of external genital warts (EGWs) in a large population remains unclear.ObjectivesTo determine epidemiologic and clinical features of patients presenting EGWs in France in the era of HPV vaccination.Patients and methodsIn this prospective, observational study, we analyzed clinical features and treatments between January 1st, 2012 and March 31, 2012 for patients consulting for EGWs at 15 STI clinics throughout France.ResultsA total of 372 men and 111 women were included; mean age 31.2 years. The women were younger than the men (31.7 and 28.9 years respectively P<0.05). Among the patients, 416 (85.7%) were heterosexual, 13 bisexual and 54 (11.2%) homosexual, including one female. Males reported more sexual partners in the last 12 months (more than 3 partners in 32.6% versus 11.9%, P<0.01). Among the men, 230 had involvement of the penis alone and 46 had involvement of the anus alone. Seventy-six patients had EGWs of the anus, and of these 26 were MSM. In females, 76 had an infection of the vulva alone and 22 co-infection of the vulva and anus. MSM and females were at higher risk than heterosexual males for anal involvement (P<0.0001 and P=0.004, respectively). Three women had been vaccinated: two with Gardasil^® and one with Cervarix^®. Cryotherapy was the preferred treatment.ConclusionWith the advent of HPV vaccination, a global strategy for the prevention and treatment of EGW should be implemented.



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Nævus comédonien : mutations somatiques de NEK9

Publication date: Available online 19 September 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): O. Dereure




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Apport de la microscopie confocale par réflectance dans le diagnostic d’érucisme oculocutané ou réaction aux poils de chenilles processionnaires

Publication date: Available online 19 September 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Perrot, R. Julienne, M. Kaspi, B. Labeille, D. Grivet, A. Vercherin, F. Cambazard, E. Cinotti




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Low-intensity laser (660 nm) on sternotomy healing in patients who underwent coronary artery bypass graft: a randomized, double-blind study

Abstract

The aim of this study was to analyze the healing effects of low-level laser therapy (LLLT) on the longitudinal sternotomy incisions of patients who underwent coronary artery bypass graft (CABG). The volunteers were randomized into three groups of equal size (n = 30): control, placebo, and laser (λ = 660 nm and spatial average energy fluency [SAEF] = 1.06 J/cm²). The patients in the laser group underwent irradiation on postoperative days 2, 4, 6, and 8, and their sternotomy incisions were photographed immediately after the surgery and 8 days later for analysis. Three researchers who were blinded to the patient treatment groups analyzed the incision photographs to assess hyperemia and wound closure on the day of hospital discharge (eighth postoperative day). The sternotomy incisions in the LLLT group demonstrated less hyperemia, incisional bleeding, and dehiscence (p ≤ 0.005).

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Effect of low-level laser therapy on angiogenesis and matrix metalloproteinase-2 immunoexpression in wound repair

Abstract

Low-level laser therapy (LLLT) induces anti-inflammatory and angiogenic activities in wound healing. However, the mechanism of action and optimal parameters require further clarification. In this study, we investigated the effects of LLLT on wound healing matrix metalloproteinase (MMP)-2 immunoexpression and angiogenic processes. Twenty female Wistar rats were randomly divided into four groups (n = 5) according to the treatments as follows. CG7 and CG14 were control groups at days 7 and 14, respectively, which received physiological saline (0.9 % NaCl daily). LG7 and LG14 were laser therapy groups at days 7 and 14, respectively, which received two (LG7) or four (LG14) LLLT applications (40 mW; 660 nm; 4 J/cm²). A dorsal skin sample in the wound area (measuring 2 cm²) was removed after the experimental period, and then the animals were euthanized. The specimens were processed for qualitative and quantitative histological analyses and measurement of MMP-2 expression in the dermis and epidermis. A persistent crust and moderate number of inflammatory cells were found in CG7 and CG14 groups. In the LG14 group, wounds demonstrated complete re-epithelization at the remodeling phase. Angiogenesis and MMP-2 expression were higher in LLLT-treated groups, particularly the LG14 group, which correlated according to the Spearman correlation test. LLLT improves wound healing by enhancing neocollagenesis, increasing the amount of new vessels formed in the tissue (neoangiogenesis), and modulating MMP-2 expression. Epidermal overexpression of MMP-2 was correlated to angiogenic processes.

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High Prevalence of Back Pain and Axial Spondyloarthropathy in Patients with Hidradenitis Suppurativa

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease, causing fistulating sinuses in the intertriginous skin of axillary, genitofemoral and perianal sites. Objective: As other chronic inflammatory diseases, e.g. psoriasis, are frequently associated with spondyloarthropathies (SpA), the goal of this study was to quantify the prevalence of back pain and SpA in HS patients. Methods: A prospective questionnaire survey in 100 HS patients and a retrospective evaluation of pelvic magnetic resonance imaging (MRI) scans in 46 HS patients were conducted. Results: 71% of HS patients were suffering from back pain. There was no difference between age at onset of HS, disease duration, body mass index (BMI), or disease severity between HS patients with and without back pain. Evaluating pelvic MRI scans, 32.6% of HS patients showed signs of chronic SpA and 39.1% signs of active SpA. Again, no significant differences between patients with/without SpA were found regarding age at time of MRI, age at onset of HS, disease duration, smoking habits, and BMI. Furthermore, there was no correlation between these parameters and the degree of SpA. Limitations: Only patients with moderate/severe HS (Hurley stage II and III) in genitofemoral/perianal sites were analysed via MRI scans. Conclusion: Back pain and SpA are very common among patients with moderate/severe HS. Neither medical history nor clinical parameters provide hints for the presence of SpA.
Dermatology

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PTPN2-deficiency exacerbates T follicular helper cell and B cell responses and promotes the development of autoimmunity

Publication date: Available online 19 September 2016
Source:Journal of Autoimmunity
Author(s): Florian Wiede, Faruk Sacirbegovic, Yew Ann Leong, Di Yu, Tony Tiganis
Non-coding single nucleotide polymorphisms that repress PTPN2 expression have been linked with the development of type 1 diabetes, rheumatoid arthritis and Crohn's disease. PTPN2 attenuates CD8⁺ T cell responses to self and prevents overt autoreactivity in the context of T cell homeostasis and antigen cross-presentation. The role of PTPN2 in other immune subsets in the development of autoimmunity remains unclear. Here we show that the inducible deletion of PTPN2 in hematopoietic compartment of adult non-autoimmune prone mice results in systemic inflammation and autoimmunity. PTPN2-deficient mice had increased inflammatory monocytes, B cells and effector T cells in lymphoid and non-lymphoid tissues and exhibited symptoms of dermatitis, glomerulonephritis, pancreatitis and overt liver disease. Autoimmunity was characterised by the formation of germinal centers in the spleen and associated with markedly increased germinal center B cells and T follicular helper (Tfh) cells and circulating anti-nuclear antibodies, inflammatory cytokines and immunoglobulins. CD8⁺ T cell proliferative responses were enhanced, and interleukin-21-induced STAT-3 signalling in Tfh cells and B cells was increased and accompanied by enhanced B cell proliferation ex vivo. These results indicate that deficiencies in PTPN2 across multiple immune lineages, including naive T cells, Tfh cells and B cells, contribute to the development of autoimmunity.



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The role of dopamine in positive and negative prediction error utilization during incidental learning – insights from Positron Emission Tomography, Parkinson’s disease and Huntington’s disease

Publication date: Available online 19 September 2016
Source:Cortex
Author(s): David Mathar, Leonora Wilkinson, Anna Holl, Jane Neumann, Lorenz Deserno, Arno Villringer, Marjan Jahanshahi, Annette Horstmann
Incidental learning of appropriate stimulus-response associations is crucial for optimal functioning within our complex environment. Positive and negative prediction errors (PEs) serve as neural teaching signals within distinct ('direct'/'indirect') dopaminergic pathways to update associations and optimize subsequent behavior. Using a computational reinforcement-learning model, we assessed learning from positive and negative PEs on a probabilistic task (Weather Prediction Task, [WPT]) in three populations that allow different inferences on the role of dopamine (DA) signals: (1) Healthy volunteers that repeatedly underwent [11C]raclopride Positron Emission Tomography, allowing for assessment of striatal DA release during learning, (2) Parkinson's disease (PD) patients tested both on and off L-DOPA medication, (3) early Huntington's disease (HD) patients, a disease that is associated with hyper-activation of the 'direct' pathway. Our results show that learning from positive and negative feedback on the WPT is intimately linked to different aspects of dopaminergic transmission. In healthy individuals, the difference in [11C]raclopride binding potential (BP) as a measure for striatal DA release was linearly associated with the positive learning rate. Further, asymmetry between baseline DA tone in the left and right ventral striatum was negatively associated with learning from positive PEs. Female patients with early HD exhibited exaggerated learning rates from positive feedback. In contrast, dopaminergic tone predicted learning from negative feedback, as indicated by an inverted-u-shaped association observed with baseline [11C]raclopride BP in healthy controls and the difference between PD patients' learning rate on and off dopaminergic medication. Thus, the ability to learn from positive and negative feedback is a sensitive marker for the integrity of dopaminergic signal transmission in the 'direct' and 'indirect' dopaminergic pathways. The present data are interesting beyond clinical context in that imbalances of dopaminergic signaling have not only been observed for neurological and psychiatric conditions but also been proposed for obesity and adolescence.



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Hedgehog signal expression in articular cartilage of rat temporomandibular joint and association with adjuvant-induced osteoarthritis

Objective

The aim of this study was to investigate the changes in hedgehog (Hh) expression and its possible effects on cartilage degeneration in adjuvant-induced temporomandibular joint osteoarthritis (TMJOA) of rats.

Methods

Forty-eight male Sprague–Dawley rats were randomly divided into experimental osteoarthritis (OA) and sham control groups. The bilateral TMJs of six rats from each group were harvested at three, seven, 14, and 28 days. Histological changes in condylar cartilage were assessed by hematoxylin and eosin, toluidine blue, and safranin O staining. The expression of Hh signal-related proteins including Indian hedgehog (Ihh), patched-1 (Ptch1), smoothened (Smo), glioma-associated oncogene homologue1 (Gli1) in cartilage was assessed by immunohistochemistry and Western blot. The protein expression of matrix metalloproteinase-13 (MMP-13), type X collagen, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) in cartilage was evaluated by Western blot.

Results

The histological analysis showed marked cartilage degeneration in adjuvant-induced OA groups, including reduced cartilage cellular density, thinner and degraded cartilage, and decreased proteoglycan content in the extracellular matrix. Compared with matched control groups, the expression of Ihh, Ptch1, Smo, and Gli1 in the OA groups was higher in a time-dependent manner. The protein levels of MMP-13, type X collagen, and ADAMTS-5 were substantially increased in OA cartilage compared with those in matched control rats.

Conclusion

These results indicate that the activation of Ihh signaling may be correlated with pathological changes of condylar cartilage in adjuvant-induced TMJOA.

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Presence and distribution of leptin and leptin receptor in the canine gallbladder

Publication date: Available online 19 September 2016
Source:Acta Histochemica
Author(s): Sungin Lee, Aeri Lee, Oh-kyeong Kweon, Wan Hee Kim
The hormone leptin is produced by mature adipocytes and plays an important role in regulating food intake and energy metabolism through its interaction with the leptin receptor. In addition to roles in obesity and obesity-related diseases, leptin has been reported to affect the components and secretion of bile in leptin-deficient mice. Furthermore, gallbladder diseases such as cholelithiasis are known to be associated with serum leptin concentrations in humans. We hypothesized that the canine gallbladder is a source of leptin and that the leptin receptor may be localized in the gallbladder, where it plays a role in regulating the function of this organ. The aim of this study was to demonstrate the presence and expression patterns of leptin and its receptors in normal canine gallbladders using reverse transcriptase-PCR (RT-PCR) and immunohistochemistry. Clinically normal gallbladder tissue samples were obtained from four healthy beagle dogs with similar body condition scores. RT-PCR and sequencing of the amplified PCR products revealed the presence of leptin mRNA and its receptors in the gallbladder. Immunohistochemical investigations demonstrated the expression of leptin and its receptors in the luminal single columnar and tubuloalveolar glandular epithelial cells. In conclusion, the results of this study demonstrated the presence of leptin and its receptors in the gallbladders of dogs. Leptin and its receptor were both localized throughout the cytoplasm of luminal and glandular epithelial cells. These results suggested that the gallbladder is not only a source of leptin, but also a target of leptin though autocrine/paracrine mechanisms. The results of this study could increase the understanding of both the normal physiological functions of the gallbladder and the pathophysiological mechanisms of gallbladder diseases characterized by leptin system dysfunction.



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Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Effects of nanoparticle on the dynamic behaviors of recycled aggregate concrete under impact loading

Publication date: 15 December 2016
Source:Materials & Design, Volume 112
Author(s): Wengui Li, Zhiyu Luo, Chu Long, Chengqing Wu, Wen Hui Duan, Surendra P. Shah
A 100mm-diameter split Hopkinson pressure bar (SHPB) was applied to investigate effects of nanoparticles on the dynamic mechanical properties of recycled aggregate concrete (RAC) under impact loading. The nano-SiO2 (NS) and nano-CaCO3 (NC) were incorporated to replace cement by mass of 1 and 2% in RACs. The impact velocities were set as 7.7, 9.8 and 11.6m/s in the SHPB tests. The effects of nanoparticles on failure patterns, compressive strengths, elastic modulus, peak strain and dynamic increase factor (DIF) of RACs under different strain rates were analyzed and discussed. The results show that nanomodified RACs exhibit higher both quasi-static and dynamic compressive strengths compared to control RAC. Dynamic elastic modulus of RAC seems not be affected by nanoparticle dosages and impact velocities. Compared to NC, NS is more effective to improve dynamic compressive strengths of RAC. On the other hand, the nanoparticles modified RACs exhibit lower DIF values than that of the control RAC. Moreover, NC obviously more reduces the DIF values of nanomodified RAC than NS.

Graphical abstract

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Riedel's thyroiditis association with IgG4-related disease

Abstract

Context

IgG4 positive (+) plasma cells have been reported in both Riedel's thyroiditis (RT) and Hashimoto's thyroiditis (HT). These cells are the hallmark of IgG4-related disease (IgG4-RD).

Objective

We sought to determine if RT is part of IgG4-RD spectrum.

Design, Setting and Patients

This was a case-control study performed at a tertiary medical center. We included RT cases from the period 1958-2008 that had sufficient paraffin-embedded tissue for IgG4 immunostaining. Controls were HT patients, age and gender matched, with similar pathology criteria.

Main Outcome Measure

The main outcome measures were the intensity of the IgG4 staining and the clinical and histological correlates with IgG4-RD.

Results

Six pairs of RT and HT were analyzed. The mean age was 44.7 years. In both groups 5/6 cases had positive IgG4 staining. The mean number of IgG4+ cells/ HPF, normalized to the degree of inflammation, was 3.2 ± 3.0 SD (RT) vs. 0.9 ± 0.7 (HT), p=0.15, for fibrotic areas and 2.1 ± 2.3 SD vs. 1.0 ± 0.8 (p=0.39) for areas with lymphoid aggregates. We found the number of IgG4+ cells in RT to be inversely correlated with the duration of disease (p=0.046). Three RT cases had associated co-morbidities from the IgG4-RD spectrum while none of the HT cases had such conditions.

Conclusions

RT is a component of IgG4-RD with the density of the IgG4+ lymphocytic infiltrate being time dependent. In this small study we did not identify differences in IgG4 infiltration between RT and HT, minimizing the utility of this marker in RT diagnosis.

This article is protected by copyright. All rights reserved.

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Adherence to treatment in men with hypogonadotropic hypogonadism

Summary

Objective

Men with congenital hypogonadotropic hypogonadism (CHH) typically require lifelong hormonal therapy and discontinuing treatment can have negative health consequences. Little is known about adherence to treatment or the psychosocial impact of CHH.

Design

A sequential, multiple methods approach was used. A quantitative online survey assessed adherence to treatment, depressive symptoms, and illness perceptions. Subsequently, qualitative focus groups explored patient-reported factors for adherence.

Patients

Adult men with CHH on at least one year of treatment were recruited internationally.

Measurements

Adherence (Morisky medication adherence scale), depressive symptoms (Zung self-rating depression scale), and patient perception of CHH (revised illness perception questionnaire) were assessed in an online survey and comparisons were made to reference groups. Patient focus group discussions were conducted and thematic analysis was employed to identify patient-reported factors for adherence.

Results

In total, 101 men on long-term treatment were included (mean age 37±11 yrs). More than half 58/101 (57%) exhibited low medication-adherence and a significantly elevated prevalence of mild, moderate, or severe depressive symptoms (27%, 17%, 20% respectively, all p<0.001 vs. reference population). Patients reported negative illness perceptions and significant psychosocial consequences. Focus group discussions (n=3, 26 total patients) identified patient-, health professional- and healthcare system- related barriers as targets for improving adherence.

Conclusions

CHH men are challenged to adhere to long-term treatment. Poor adherence may contribute to adverse effects on bone, sexual and psychological health. The psychosocial morbidity of CHH is significant and appears to be underappreciated by healthcare providers.

This article is protected by copyright. All rights reserved.

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Glypican-3 distinguishes aggressive from non-aggressive odontogenic tumors: A preliminary study

Abstract

Background

Glypican-3 is a cell suface proteoglycan that is found in embrionary tissues and there are no studies investigating this protein in odontogenic tumor. Thus, the aim of this study was investigate glypican-3 in a series of agressive and non-aggressive odontogenic tumors.

Methods

Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, 4 unicystic ameloblastoma, 28 KOTs including 5 associated with Gorlin-Goltz syndrome) and non-aggressive odontogenic tumors (5 adenomatoid odontogenic tumors, and 2 calcifying cystic odontogenic tumors) and analyzed for glypican-3 using immunohistochemistry.

Results

Glypican-3 was observed in seven solid ameloblastoma and eighteen keratocystic odontogenic tumor including three of the five syndromic cases, but there was no significant difference between syndromic and sporadic cases (p>0,05; Fisher's exact Test). All cases of unicystic ameloblastoma (n=4), adenomatoid odontogenic tumor (n=5) and calcifying cystic odontogenic tumor (n=2) were negative.

Conclusions

This provided insights into the presence of glypican-3 in odontogenic tumors. This protein distinguished aggressive from non-aggressive odontogenic tumors.

This article is protected by copyright. All rights reserved.

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Brain pathology case of the month – July 2016 – Case 1 36-Year-Old man with parietal scalp mass

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Brain pathology case of the month August 2016 – case 2 A 71 year old man presenting with headache, blurry vision and alexia without agraphia

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Brain pathology case of the month - July 2016 – case 2 A 49-Year-old man with progressive cranial neuropathies

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Brain pathology case of the month August 2016 Case 1 A 37-Year-Old pregnant female with multifocal brain lesions

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iNOS expression is increased in the alveolar compartment of asthmatic patients

Abstract

Increased exhaled nitric oxide (NO) levels in asthma is suggested to be through inducible NO synthase (iNOS). The aim of this study was to investigate the expression of iNOS in BAL cells and tissue from central and peripheral airways and compare it with the exhaled bronchial and alveolar NO levels in asthmatic patients versus a control group.

Methods

Thirty-two asthmatic patients (defined as controlled or uncontrolled according to Asthma Control Test score cut-off: 20) and eight healthy controls were included. Exhaled NO was measured and alveolar concentration and bronchial flux were calculated. iNOS was measured in central and peripheral lung biopsies, as well as BAL cells. BAL macrophages were stimulated in vitro, and iNOS expression and NO production were investigated.

Results

Expression of iNOS was increased in central airway tissue and the alveolar compartment in uncontrolled as compared to controlled asthma and healthy controls. There were no differences, however, in iNOS mRNA levels in total BAL cells in uncontrolled as compared to controlled asthma. BAL cell mRNA levels of iNOS or iNOS expression in central and alveolar tissue did not relate to alveolar NO, nor to bronchial flux of NO. In vitro stimulation with leukotrieneD₄ increased iNOS mRNA levels and NO production in cultured BAL macrophages.

Conclusion

The levels of both bronchial and alveolar iNOS are increased in uncontrolled as compared to controlled asthma. However, levels of iNOS in BAL macrophages were not reflected by alveolar NO. Both central and distal iNOS levels may reflect responsiveness to steroid treatment.

This article is protected by copyright. All rights reserved.

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Immunopathology alters Th17 cell glucocorticoid sensitivity

Abstract

Th17 cells contribute to several inflammatory conditions and increasing evidence supports that Th17 cells are glucocorticoid resistant. However, Th17 cells in psoriasis and related diseases are glucocorticoid sensitive. We compare glucocorticoid sensitive and resistant immunological diseases and suggest that several aspects in Th-17 related diseases alter glucocorticoid sensitivity of Th17 cells. We identify molecular pathways that are implicated in glucocorticoid sensitivity of Th17 cells in the literature, as this information is useful for developing approaches to overcome glucocorticoid-resistant immunopathology.

This article is protected by copyright. All rights reserved.

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Erratum

Dermatology 2016;232:522

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Stretch Mark Removal: Treatments and Home Remedies

Stretch marks are a common problem affecting men and women of nearly all ages and skin types. Learn about the treatments and home remedies for them here.

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Sequential development of hepatocellular carcinoma and liver angiosarcoma in a vinyl chloride–exposed worker

Publication date: November 2016
Source:Human Pathology, Volume 57
Author(s): Maria Guido, Samantha Sarcognato, Guido Pelletti, Matteo Fassan, Bruno Murer, Rossella Snenghi
Strong experimental and clinical evidences have definitely linked occupational vinyl chloride exposure to development of angiosarcoma of the liver. In contrast, despite the International Agency for Research on Cancer having included vinyl chloride among the causes of hepatocellular carcinoma, the association between vinyl chloride exposure and hepatocellular carcinoma remains debated. This issue is relevant, because occupational exposure to high levels of vinyl chloride may still occur. We report a unique case of sequential occurrences of hepatocellular carcinoma and angiosarcoma of the liver, in a vinyl chloride–exposed worker without cirrhosis and any known risk factor for chronic liver disease. Both the hepatocellular carcinoma and the surrounding normal liver showed micronucleus formation, which reflects genotoxic effect of vinyl chloride. Angiosarcoma showed a KRAS G12D point mutation, which is considered to be characteristic of vinyl chloride–induced angiosarcoma. This case supports the pathogenic role of vinyl chloride in both hepatocellular carcinoma and angiosarcoma development.



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Cerebellar Control of Eye Movements.

Background: The cerebellum plays a central role in the online, real-time control, and long-term modulation of eye movements. Evidence acquisition: We reviewed the latest (fifth) edition of Leigh and Zee's textbook, The Neurology of Eye Movements, and literature in PUBMED using the following terms: cerebellum, flocculus, paraflocculus, vermis, oculomotor vermis, dorsal vermis, caudal fastigial nucleus, fastigial oculomotor region, uvula, nodulus, ansiform lobule, eye movements, saccades, ipsipulsion, contrapulsion, smooth pursuit, vergence, convergence, divergence, gaze-holding, down beat nystagmus, vestibulo-ocular reflex (VOR), angular VOR, translational VOR, skew deviation, velocity storage. Results: The cerebellum is vital in optimizing the performance of all classes of gaze-shifting and gaze-stabilizing reflexes. The flocculus-paraflocculus are crucial to VOR gain and direction, pulse-step matching for saccades, pursuit gain, and gaze-holding. The oculomotor vermis and caudal fastigial nuclei are essential in saccadic adaptation and accuracy, and pursuit gain. The nodulus and ventral uvula are involved in processing otolothic signals and VOR responses, including velocity storage. Conclusions: The cerebellum guarantees the precision of ocular movements to optimize visual performance and occupies a central role in all classes of eye movements both in real-time control and in long-term calibration and learning (i.e., adaptation). (C) 2016 by North American Neuro-Ophthalmology Society

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