Τετάρτη, 24 Μαΐου 2017

Maxillary resection for cancer, zygomatic implants insertion, and palatal repair as single-stage procedure: report of three cases



Oronasal/antral communication, loss of teeth and/or tooth-supporting bone, and facial contour deformity may occur as a consequence of maxillectomy for cancer. As a result, speaking, chewing, swallowing, and appearance are variably affected. The restoration is focused on rebuilding the oronasal wall, using either flaps (local or free) for primary closure, either prosthetic obturator. Postoperative radiotherapy surely postpones every dental procedure aimed to set fixed devices, often makes it difficult and risky, even unfeasible. Regular prosthesis, tooth-bearing obturator, and endosseous implants (in native and/or transplanted bone) are used in order to complete dental rehabilitation. Zygomatic implantology (ZI) is a valid, usually delayed, multi-staged procedure, either after having primarily closed the oronasal/antral communication or after left it untreated or amended with obturator.

The present paper is an early report of a relatively new, one-stage approach for rehabilitation of patients after tumour resection, with palatal repair with loco-regional flaps and zygomatic implant insertion: supposed advantages are concentration of surgical procedures, reduced time of rehabilitation, and lowered patient discomfort.

Cases presentation

We report three patients who underwent alveolo-maxillary resection for cancer and had the resulting oroantral communication directly closed with loco-regional flaps. Simultaneous zygomatic implant insertion was added, in view of granting the optimal dental rehabilitation.


All surgical procedures were successful in terms of oroantral separation and implant survival. One patient had the fixed dental restoration just after 3 months, and the others had to receive postoperative radiotherapy; thus, rehabilitation timing was longer, as expected. We think this approach could improve the outcome in selected patients.


Revisiting radial forearm free flap for successful venous drainage


Tissue defect reconstruction using radial forearm free flap (RFFF) is a common surgical technique whose success or failure is mainly dependent on venous drainage. RFFF has two major venous outflow systems, superficial and deep vein. Drainage methods include combining both systems or using one alone. This review aims to recapitulate the vascular anatomy and network of RFFF as well as shed light on deep vein as a reliable venous drainage system. We also discuss basic evidence for and advantages of single microanastomosis with coalesced vein to overcome technical difficulties associated with the deep vein system.


Olfactory neuroblastoma: a single-center experience


Olfactory neuroblastoma (ONB) is a potentially curable disease, despite being an aggressive malignancy with a poor natural history. Our goal was to evaluate management outcomes for patients with ONB treated at our institution. Our prospective database for brain tumors and the pathology registry of head and neck cancers at Oslo University Hospital were searched to identify all patients treated for ONB between 1998 and 2016. Variables extracted from these databases, supplemented by retrospective chart reviews, underwent thorough analysis. All cases were formally re-examined by a dedicated head and neck pathologist. Twenty patients were identified. Follow-up was 100%. Mean follow-up was 81.5 months for the entire cohort and 120.3 months for patients with no evidence of disease. Fourteen patients underwent treatment of choice including craniofacial resection (CFR) with or without radiotherapy (XRT). Six patients could only receive less extensive treatment; three patients underwent lateral rhinotomy (LR) with or without XRT after being deemed medically unsuitable for CFR, while another three patients received only supportive, non-surgical treatment (due to positive lymph node status in two and to extensive tumor size in one case). Overall and disease-specific survival rates were 100% after 10 years of follow-up when negative surgical margins were achieved by CFR. Positive margins were associated with poorer outcome with no patients surviving longer than 44 months. Long-term survival was also achieved in two cases among patients not eligible for CFR: one case after radical LR and one case after radio-chemotherapy. Advanced disease at presentation (tumor size ≥40 mm, Kadish grades C and D, or TNM IVa and IVb) and positive surgical margins were correlated to significantly dismal survival. Our study suggests that CFR with or without adjuvant XRT is safe and leads to excellent long-time overall and disease-specific survival. Negative surgical margins, tumor size <40 mm, Kadish stage A/B, and TNM stages I-III are independent prognostic predictors of outcome.


PROPIONIBACTERIUM ACNES AND CHRONIC DISEASES : P. acnes is an opportunistic pathogen, causing a range of postoperative and device-related infections e.g., surgery,post-neurosurgical infection,joint prostheses, shunts and prosthetic heart valves. P. acnes may play a role in other conditions, including inflammation of the prostate leading to cancer,SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) syndrome, sarcoidosis and sciatica.

P. acnes bacteria live deep within follicles and pores, away from the surface of the skin. In these follicles, P. acnes bacteria use sebum, cellular debris and metabolic byproducts from the surrounding skin tissue as their primary sources of energy and nutrients. Elevated production of sebum by hyperactive sebaceous glands (sebaceous hyperplasia) or blockage of the follicle can cause P. acnes bacteria to grow and multiply.[6]

P. acnes bacteria secrete many proteins, including several digestive enzymes.[7] These enzymes are involved in the digestion of sebum and the acquisition of other nutrients. They can also destabilize the layers of cells that form the walls of the follicle. The cellular damage, metabolic byproducts and bacterial debris produced by the rapid growth of P. acnes in follicles can trigger inflammation.[8] This inflammation can lead to the symptoms associated with some common skin disorders, such as folliculitis and acne vulgaris.[9][10][11]

The damage caused by P. acnes and the associated inflammation make the affected tissue more susceptible to colonization by opportunistic bacteria, such as Staphylococcus aureus. Preliminary research shows healthy pores are only colonized by P. acnes, while unhealthy ones universally include the nonpore-resident Staphylococcus epidermidis, amongst other bacterial contaminants. Whether this is a root causality, just opportunistic and a side effect, or a more complex pathological duality between P. acnes and this particular Staphylococcus species is not known.[12]

P. acnes has also been found in corneal ulcers, and is a common cause of chronic endophthalmitis following cataract surgery. Rarely, it infects heart valves leading to endocarditis, and infections of joints (septic arthritis) have been reported.[5] Furthermore, Propionibacterium species have been found in ventriculostomy insertion sites, and areas subcutaneous to suture sites in patients who have undergone craniotomy. It is a common contaminant in blood and cerebrospinal fluid cultures.

P. acnes has been found in herniated discs.[13] The propionic acid which it secretes creates micro-fractures of the surrounding bone. These micro-fractures are sensitive and it has been found that antibiotics have been helpful in resolving this type of low back pain.[14]

P. acnes can be found in bronchoalveolar lavage of approximately 70% of patients with sarcoidosis and is associated with disease activity, but it can be also found in 23% of controls.[15][16] The subspecies of P. acnes that cause these infections of otherwise sterile tissues (prior to medical procedures), however, are the same subspecies found on the skin of individuals who do not have acne-prone skin, so are likely local contaminants. Moderate to severe acne vulgaris appears to be more often associated with virulent strains.[17]

P. acnes is an opportunistic pathogen, causing a range of postoperative and device-related infections e.g., surgery,[18] post-neurosurgical infection,[19] joint prostheses, shunts and prosthetic heart valves. P. acnes may play a role in other conditions, including inflammation of the prostate leading to cancer,[20] SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) syndrome, sarcoidosis and sciatica.[21]

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Dichotic Listening Deficit Associated With Solvent Exposure.Due to their lipophilic nature, solvents can adversely affect large white matter tracks such as the corpus callosum. Previous investigations reveal that long-term workplace exposure to solvents is also deleterious to various auditory processes.

Dichotic Listening Deficit Associated With Solvent Exposure.
από Landry, Simon P.; Fuente, Adrian στο Otology & Neurotology Published Ahead-of-Print
Μετάφραση άρθρου
Hypothesis: A significant left ear deficit can be observed in solvent-exposed individuals using the dichotic digit test. Background: Solvents are ubiquitous in global industrial processes. Due to their lipophilic nature, solvents can adversely affect large white matter tracks such as the corpus callosum. Previous investigations reveal that long-term workplace exposure to solvents is also deleterious to various auditory processes. Investigations in exposed populations suggest a decreased performance for dichotic listening. Methods: In this present study, we examined the lateralization of a dichotic digit test score for 49 solvent-exposed individuals along with 49 age- and sex-matched controls. We evaluated group differences between test scores and the right ear advantage using a laterality index (LI). Results: Individual ear results suggest that long-term workplace solvent exposure is associated with a significantly lower dichotic listening score for the left ear. A binaural compound score analysis using a laterality index supports this left-ear deficit. Conclusion: These results provide an insight on the effects of solvent exposure on dichotic listening abilities. Further research should investigate the importance of using dichotic listening tasks to screen for solvent-induced auditory dysfunction in exposed individuals. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Epstein-Barr virus, human endogenous retroviruses (HERVs) and human herpesvirus 6 (HHV-6) but also less common viruses such as Saffold and measles viruses are associated with multiple sclerosis

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos

Study of Heavy Metal Accumulation and Residual Toxicity in Soil Saturated with Phosphate Processing Wastewater


The effects of phosphate processing wastewater (PPWW) on heavy metal accumulation in a Mediterranean soil (Tunisia, North Africa) were investigated. Moreover, the residual toxicities of PPWW-irrigated soils extracts were assessed. Results showed that heavy metal accumulation was significantly higher in PPWW-irrigated soil extracts than in control soil. The heavy metal accumulation increased over time in treated soil samples and their average values followed the following order: Iron (Fe 252.72 mg l−1) > Zinc (Zn 152.95 mg l−1) > Lead (Pb 128.35 mg l−1) > Copper (Cu 116.82 mg l−1) > Cadmium (Cd 58.03 mg l−1). The residual microtoxicity and phytotoxicity of the various treated soil samples extracts were evaluated by monitoring the bioluminescence inhibition (BI %) of Vibrio ficheri and the measurement of the germination indexes (GI %) of Lepidium sativum and Medicago sativa seeds. The results showed an important increase of residual toxicities of PPWW-treated soil extracts over time.


Effect of Biochar Amendment and Ageing on Adsorption and Degradation of Two Herbicides


Biochar amendment can alter soil properties, for instance, the ability to adsorb and degrade different chemicals. However, ageing of the biochar, due to processes occurring in the soil over time, can influence such biochar-mediated effects. This study examined how biochar affected adsorption and degradation of two herbicides, glyphosate (N-(phosphonomethyl)-glycine) and diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) in soil and how these effects were modulated by ageing of the biochar. One sandy and one clayey soil that had been freshly amended with a wood-based biochar (0, 1, 10, 20 and 30% w/w) were studied. An ageing experiment, in which the soil-biochar mixtures were aged for 3.5 months in the laboratory, was also performed. Adsorption and degradation were studied in these soil and soil-biochar mixtures, and compared to results from a soil historically enriched with charcoal. Biochar amendment increased the pH in both soils and increased the water-holding capacity of the sandy soil. Adsorption of diuron was enhanced by biochar amendment in both soils, while glyphosate adsorption was decreased in the sandy soil. Ageing of soil-biochar mixtures decreased adsorption of both herbicides in comparison with freshly biochar-amended soil. Herbicide degradation rates were not consistently affected by biochar amendment or ageing in any of the soils. However, glyphosate half-lives correlated with the Freundlich Kf values in the clayey soil, indicating that degradation was limited by availability there.


Leaching of PCE-based Superplasticiser from Microfine Cement: a Chemical and Ecotoxicological Point of View


The construction materials industry faces major challenges since 2013 when the European Construction Products Regulation was implemented, especially in the sector of environmentally friendly construction products. This study determined concentrations of leachable inorganic and organic compounds from microfine cement paste with and without superplasticiser addition. Furthermore, the leached superplasticiser amounts were detected via LC-MS. The multi-method approach was supplemented by ecotoxicological assays. Phytotoxicity was tested with white mustard (Sinapis alba) and cress (Lepidium sativum). The mutagenic and genotoxic potential of the leachates was tested with the Ames fluctuation assay and the umuC assay. As leaching protocol, the European horizontal dynamic surface leaching test was used. The cement paste samples with superplasticiser followed the wash-off effect with a total organic carbon release up to 43 mmol/m2, whereas the release of samples without superplasticiser was driven by diffusion. The ecotoxicological assays showed a clear time depending behaviour. No cytotoxicity and mutagenicity could be observed; anyhow some leachates show minor genotoxic potential. In all tests, a clear difference between the samples with and without superplasticiser could be detected.

This study clearly demonstrates the importance of further studies in the field of leaching of construction products.


A Population Pharmacokinetic and Pharmacodynamic Analysis of Abemaciclib in a Phase I Clinical Trial in Cancer Patients


Background and Objectives

Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated clinical activity in a number of different cancer types. The objectives of this study were to characterize the pharmacokinetics of abemaciclib in cancer patients using population pharmacokinetic (popPK) modeling, and to evaluate target engagement at clinically relevant dose levels.


A phase I study was conducted in cancer patients which incorporated intensive pharmacokinetic sampling after single and multiple oral doses of abemaciclib. Data were analyzed by popPK modeling, and patient demographics contributing to pharmacokinetic variability were explored. Target engagement was evaluated by combining the clinical popPK model with a previously developed pre-clinical pharmacokinetic/pharmacodynamic model.


The pharmacokinetic analysis incorporated 4012 plasma concentrations from 224 patients treated with abemaciclib at doses ranging from 50 to 225 mg every 24 h and 75 to 275 mg every 12 h. A linear one-compartment model with time- and dose-dependent relative bioavailability (F rel) adequately described the pharmacokinetics of abemaciclib. Serum albumin and alkaline phosphatase were the only significant covariates identified in the model, the inclusion of which reduced inter-individual variability in F rel by 10.3 percentage points. By combining the clinical popPK model with the previously developed pre-clinical pharmacokinetic/pharmacodynamic model, the extent of target engagement in skin in cancer patients was successfully predicted.


The proportion of abemaciclib pharmacokinetic variability that can be attributed to patient demographics is negligible, and as such there are currently no dose adjustments recommended for adult patients of different sex, age, or body weight.

Trial registration

NCT01394016 (ClinicalTrials.gov).


In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents


Background and Objectives

Long-acting injectable antiretrovirals represent a pharmacological alternative to oral formulations and an innovative clinical option to address adherence and reduce drug costs. Clinical studies in children and adolescents are characterised by ethical and logistic barriers complicating the identification of dose optimisation. Physiologically-based pharmacokinetic modelling represents a valuable tool to inform dose finding prior to clinical trials. The objective of this study was to simulate potential dosing strategies for existing long-acting injectable depot formulations of cabotegravir and rilpivirine in children and adolescents (aged 3–18 years) using physiologically-based pharmacokinetic modelling.


Whole-body physiologically-based pharmacokinetic models were developed to represent the anatomical, physiological and molecular processes and age-related changes in children and adolescents through allometric equations. Models were validated for long-acting injectable intramuscular cabotegravir and rilpivirine in adults. Subsequently, the anatomy and physiology of children and adolescents were validated against available literature. The optimal doses of monthly administration of cabotegravir and rilpivirine were identified in children and adolescents, to achieve trough concentrations over the target concentrations derived in a recent efficacy trial of the same formulations.


Pharmacokinetic data generated through the physiologically-based pharmacokinetic simulations were similar to observed clinical data in adults. Optimal doses of long-acting injectable antiretrovirals cabotegravir and rilpivirine were predicted using the release rate observed for existing clinical formulations, for different weight groups of children and adolescents. The intramuscular loading dose and maintenance dose of cabotegravir ranged from 200 to 600 mg and from 100 to 250 mg, respectively, and for rilpivirine it ranged from 250 to 550 mg and from 150 to 500 mg, respectively, across various weight groups of children ranging from 15 to 70 kg.


The reported findings represent a rational platform for the identification of suitable dosing strategies and can inform prospective clinical investigation of long-acting injectable formulations in children and adolescents.


Tick-borne disease

Tick-borne disease: A disease carried by or caused by a tick. The tick-borne diseases in the US include:

Anyone working in the outdoors, especially in areas with tall grasses, shrubs, low hanging branches, or leaf mold is susceptible to being bitten by a tick. Ticks do not jump, crawl, or fall onto a person. They are picked up when your clothing or hair brushes a leaf or other object they are on. Ticks are generally found within three feet of the ground. Once picked up, they will crawl until they find a likely site to feed. Often they will find a spot at the back of a knee, near the hairline, or behind the ears.

The best way to prevent tick borne diseases is not to be being bitten by a tick. There are several things you can do which will lessen your chance of being bitten.

  • Wear long pants and a long sleeved shirt, tuck the shirt into your pants, tuck the pants into your socks or boots or use tape to close the opening were they meet
  • Wear a hat, tie back long hair
  • Use an EPA approved insect repellant or arachnicide (pesticide) which is effective for ticks, such as DEET (N,N-diethyl-m-toluamide) or pyrethrin. Be sure and follow all precautionary information, and be aware that some people are sensitive to these chemicals.
  • Wear light colored clothing so that a tick can be seen better.
  • Change clothes when you return from a area where ticks may be located.
  • Shower to wash off any loose ticks.

Check for ticks and remove them properly:

  • Check clothing for ticks on a frequent basis.
  • If you find a tick, do a more thorough tick check. When you return from an area where ticks may be located, check all of your body for ticks. It may be helpful to have someone else check your back or other areas which are difficult to see. Be sure to include:
    • Parts that bend (back of knee, between fingers and toes, underarms).
    • Pressure points where clothing presses against skin (underwear elastic, belts, neck).
    • Other common areas (belly button, around or in ear, hairline, top of head).
  • Once inside do a final thorough tick check and clothing change.
  • If you are in a tick infested area or an area known to have disease carrying ticks, perform the checks on a more regular basis.
  • Remove unattached ticks promptly.
  • Attached ticks are promptly removed using fine pointed tweezers:
    • The mouth parts of the tick are grasped with the tweezers as close to the skin as possible;
    • Apply firm steady pressure upward until the tick releases - do not jerk, twist, squash or squeeze the tick;
    • Clean the wound and the tweezers with an antiseptic.
    • Do not use petroleum jelly or nail polish remover, or prick or burn the tick, these actions can cause infected juices to enter the wound.

Place clothing worn in tick infested areas in the dryer for at least 30 minutes in order to kill any ticks. Be sure and check pets and other animals for ticks. Use approved tick repellents or products which kill ticks. If you want to have the tick checked for disease, place the tick in a clean vial or ziplock bag with a blade of grass, then contact your State Health Department for more information.

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Exploiting Pharmacokinetic Models of Tamoxifen and Endoxifen to Identify Factors Causing Subtherapeutic Concentrations in Breast Cancer Patients


Background and Objectives

A better understanding of the highly variable pharmacokinetics (PK) of tamoxifen and its active metabolite endoxifen in breast cancer patients is crucial to support individualised treatment. This study used a modelling and simulation approach to quantitatively assess the influence of cytochrome P450 (CYP) 2D6 activity and other relevant factors on tamoxifen and endoxifen PK to identify subgroups at risk for subtherapeutic endoxifen concentrations.


Simulations were performed using two previously published PK models jointly describing tamoxifen and endoxifen with CYP2D6 and CYP3A4/5 enzyme activities implemented as covariates. Steady-state predictions were compared between models and with the literature values. Factors potentially causing between-model discrepancies were explored. A previously published threshold (6 ng/mL) was used to identify patients with subtherapeutic endoxifen concentrations and to perform a dose adaptation study.


Steady-state predictions of tamoxifen and endoxifen were considerably different between the models. The factors, differences in sampling time, adherence and bioavailability, were not able to fully capture between-model variability. Endoxifen steady-state fluctuations within a dosing interval were minimal (<6%). Poor (97%) and intermediate (54%) CYP2D6 metabolisers failed to achieve therapeutic endoxifen concentrations, suggesting adapted doses of tamoxifen 80 and 40 mg, respectively, achieving therapeutic endoxifen concentrations in 89.7% of patients (standard dosing 45.2%). However, interindividual variability remained.


To achieve therapeutic endoxifen concentrations early in treatment, it is advisable to initiate treatment by CYP2D6 genotype/phenotype-guided dosing, followed by therapeutic drug monitoring at steady-state. We strongly advocate to adequately measure, report and prospectively investigate influential factors (i.e. adherence, bioavailability, time to PK steady-state) in clinical trials.


Quantitative Phospho-proteomic Analysis of TNF{alpha}/NF{kappa}B Signaling Reveals a Role for RIPK1 Phosphorylation in Suppressing Necrotic Cell Death [Research]

TNFα is a potent inducer of inflammation due to its ability to promote gene expression, in part via the NFB pathway. Moreover, in some contexts, TNFα promotes Caspase-dependent apoptosis or RIPK1/RIPK3/MLKL-dependent necrosis. Engagement of the TNF Receptor Signaling Complex (TNF-RSC), which contains multiple kinase activities, promotes phosphorylation of several downstream components, including TAK1, IKKα/IKKβ, IBα, and NFB. However, immediate downstream phosphorylation events occurring in response to TNFα signaling are poorly understood at a proteome-wide level. Here we use Tandem Mass Tagging-based proteomics to quantitatively characterize acute TNFα-mediated alterations in the proteome and phosphoproteome with or without inhibition of the cIAP-dependent survival arm of the pathway with a SMAC mimetic. We identify and quantify over 8,000 phosphorylated peptides, among which are numerous known sites in the TNF-RSC, NFB, and MAP kinase signaling systems, as well as numerous previously unrecognized phosphorylation events. Functional analysis of S320 phosphorylation in RIPK1 demonstrates a role for this event in suppressing its kinase activity, association with CASPASE-8 and FADD proteins, and subsequent necrotic cell death during inflammatory TNFα stimulation. This study provides a resource for further elucidation of TNFα-dependent signaling pathways.

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Systematic Evaluation of Protein Reduction and Alkylation Reveals Massive Unspecific Side Effects by Iodine-containing Reagents [Research]

Reduction and alkylation of cysteine residues is part of virtually any proteomics workflow. Despite its frequent use, up to date no systematic investigation of the impact of different conditions on the outcome of proteomics studies has been performed. In this study, we compared common reduction reagents (dithiothreitol, tris-(2-carboxyethyl)-phosphine, and beta-mercaptoethanol) and alkylation reagents (iodoacetamide, iodoacetic acid, acrylamide, and chloroacetamide). Using in-gel digests as well as SAX fractionated in-solution digests of cytosolic fractions of HeLa cells, we evaluated 13 different reduction and alkylation conditions resulting in considerably varying identification rates. We observed strong differences in offsite alkylation reactions at 7 amino acids as well as at the peptide N-terminus, identifying single and double adducts of all reagents. Using dimethyl labeling, mass tolerant searches, and synthetic peptide experiments, we identified alkylation of methionine residues by iodine-containing alkylation reagents as one of the major factors for the differences. We observed differences of more than 9 fold in numbers of identified methionine-containing peptide spectral matches for in-gel digested samples between iodine- and non-iodine-containing alkylation reagents. This was due to formation of carbamidomethylated and carboxymethylated methionine side chains and a resulting prominent neutral loss during ESI ionization or in MS/MS fragmentation, strongly decreasing identification rates of methionine-containing peptides. We achieved best results with acrylamide as alkylation reagent, while the highest numbers of peptide spectral matches were obtained when reducing with dithiothreitol and beta-mercaptoethanol for the in-solution and the in-gel digested samples, respectively.

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Radiomics-Based Assessment of Radiation-Induced Lung Injury after Stereotactic Body Radiotherapy

Radiation-induced lung injury is common after stereotactic body radiotherapy (SBRT). For the first time, we characterized post-SBRT lung injury using computed tomography (CT)-based radiomics for 14 patients. Radiomic features significantly correlated with radiation oncologist-scored lung injury and showed significant dose-response relationships, suggesting the potential for radiomics to provide a quantitative, objective measurement of post-SBRT lung injury.

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A randomized phase II study comparing nivolumab with carboplatin-pemetrexed for patients with EGFR mutation–positive nonsquamous non–small cell lung cancer who acquire resistance to tyrosine kinase inhibitors not due to a secondary T790M mutation: rationale and protocol design for the WJOG8515L study

Antibodies to programmed cell death–1 (PD-1) such as nivolumab have shown promising clinical activity in patients with advanced non–small cell lung cancer (NSCLC), but their efficacy appears to be less pronounced in patients with such tumors harboring epidermal growth factor receptor gene (EGFR) mutations. Recent findings suggest that patients with EGFR mutation–positive NSCLC who develop resistance to tyrosine kinase inhibitors (TKIs) due to mechanisms other than acquisition of the secondary T790M mutation of EGFR are more likely to benefit from nivolumab treatment, possibly as a result of a higher level of expression of the PD-1 ligand PD-L1, than are T790M-positive patients.

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An evaluation of oxidative and nitrosative stress in children-who-stutter and its relationship to severity

Although there has been much research into the cause of stuttering, it has not yet been fully clarified. There is known to be a close relationship between stress severity and stuttering. The aim of this study was to evaluate the levels of oxidative and nitrosative stress by comparing a stuttering group and a control group. It was also aimed to evaluate the relationship between the oxidative and nitrosative stress levels and the severity of the stutter.

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“Local effects of epidermal growth factor on the wound healing in esophageal anastomosis: An experimental study”

In this study with the experimental model of primary repair of esophageal atresia(EA), we investigated the effects of the epidermal growth factor(EGF) on wound healing in the anastomosis of EA.

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Decisional regret following ventilation tube insertion

The purpose of this study was to see if parental regret following ventilation tube (VT) insertion was related to non-resolution of ear infections and thus ongoing need for otolaryngological care and VT reinsertion.

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Speech-evoked auditory brainstem responses in children with hearing loss

The main objective of the present study was to investigate subcortical auditory processing in children with sensorineural hearing loss.

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Safety and outcomes of aspirin desensitization for aspirin-exacerbated respiratory disease: a single center study

Aspirin desensitization is an effective treatment option for aspirin-exacerbated respiratory disease (AERD). Aspirin desensitization protocol modifications have improved the safety and efficiency of this procedure, yet some providers remain reluctant to perform it.

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Molecular diagnostics and lack of clinical allergy in helminth-endemic areas in Indonesia

Allergen microarray characterization of sensitization to common allergen sources in a helminth-endemic area of Indonesia shows that helminth induced cross-reactivity to cross-reactive carbohydrate determinants (CCD), and not primary sensitization to their major allergens, is the dominant feature.

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Abstracts from the 3rd International Severe Asthma Forum (ISAF)

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Sensory recovery of the breast after innervated and non-innervated autologous breast reconstructions: A systematic review

The sensory recovery of the reconstructed breast is an undervalued topic in the field of autologous breast reconstruction. The aim of this systematic review was to evaluate the available literature on the sensory recovery of the breast after innervated and non-innervated autologous breast reconstructions and to assess the possible benefits of sensory nerve coaptation compared to spontaneous reinnervation of the flap.

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A Transcription Factor IIA Binding Site Differentially Regulates RNA Polymerase II-Mediated Transcription in a Promoter Context-dependent Manner [Gene Regulation]

RNA polymerase II polymerase II (pol II) is required for the transcription of all protein-coding genes and as such represents a major enzyme whose activity is tightly regulated. Transcriptional initiation therefore requires numerous general transcriptional factors and cofactors that associate with pol II at core promoter to form a pre-initiation complex. Transcription factor IIA (TFIIA) is a general cofactor that binds TFIID and stabilizes the TFIID-DNA complex during transcription initiation. Previous studies showed that TFIIA can make contact with the DNA sequence upstream or downstream of the TATA-box, and that the region bound by TFIIA could overlap with the elements recognized by another factor, TFIIB, at adenovirus major late core promoter. Whether core promoters contain a DNA motif recognized by TFIIA remains unknown. Here we have identified a core promoter element upstream of the TATA box that is recognized by TFIIA. A search of the human promoter database revealed that many natural promoters contain a TFIIA recognition element (IIARE). We show that the IIARE enhances TFIIA-promoter binding and enhances the activity of TATA-containing promoters, but represses or activates promoters that lack a TATA box. Chromatin immunoprecipitation assays revealed that the IIARE activates transcription by increasing the recruitment of pol II, TFIIA, TAF4 and p300 at TATA-dependent promoters. These findings extend our understanding of the role of TFIIA in transcription, and provide new insights into the regulatory mechanism of core promoter elements in gene transcription by pol II.

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Protein Kinase C ϵ Stabilizes {beta}-Catenin and Regulates Its Subcellular Localization in Podocytes [Signal Transduction]

Kidney disease has been linked to dysregulated signaling via protein kinase C (PKC) in kidney cells such as podocytes. PKCα is a conventional isoform of PKC and a well-known binding partner of β-catenin, which promotes its degradation. β-Catenin is the main effector of the canonical Wnt pathway and is critical in cell adhesion. However, whether other PKC isoforms interact with β-catenin has not been studied systematically. Here we demonstrate that PKCε-deficient mice, which develop proteinuria and glomerulosclerosis, display a lower β-catenin expression compared to PKC wildtype mice, consistent with an altered phenotype of podocytes in culture. Remarkably, β-catenin showed a reversed subcellular localization pattern: while β-catenin exhibited a perinuclear pattern in undifferentiated wild-type cells, it predominantly localized to the nucleus in PKCε-knockout cells. Phorbol 12-myristate 13-acetate stimulation of both cell types revealed that PKCε positively regulates β-catenin expression and stabilization in a glycogen synthase kinase-3β independent manner. Further, β-catenin overexpression in PKCε-deficient podocytes could restore the wildtype phenotype, similar to the rescue with a PKCε construct. This effect was mediated by upregulation of P-cadherin and the β-catenin downstream target fascin1. Zebrafish studies indicated three PKCε-specific phosphorylation sites in β-catenin that are required for full β-catenin function. Co-immunoprecipitation and pulldown assays confirmed PKCε and β-catenin as binding partners and revealed that ablation of the three PKCε phosphorylation sites weakens their interaction. In summary, we identified a novel pathway for regulation of β-catenin levels and define PKCε as an important β-catenin interaction partner and signaling opponent of other PKC isoforms in podocytes.

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Proteolytic Cleavage Orchestrates Cofactor Insertion and Protein Assembly in [NiFe]-hydrogenase Biosynthesis [Molecular Biophysics]

Metalloenzymes catalyze complex and essential processes such as photosynthesis, respiration, and nitrogen fixation. For example, bacteria and archaea use [NiFe]-hydrogenases to catalyze the uptake and release of molecular hydrogen (H2). [NiFe]-hydrogenases are redox enzymes composed of a large subunit that harbors a NiFe(CN)2CO metallo-center and a small subunit with three iron-sulfur clusters. The large subunit is synthesized with a C-terminal extension, cleaved off by a specific endopeptidase during maturation. The exact role of the C-terminal extension has remained elusive, however, cleavage takes place exclusively after assembly of the [NiFe]-cofactor and before large and small subunits form the catalytically active heterodimer. To unravel the functional role of the C-terminal extension, we used an enzymatic in vitro maturation assay that allows synthesizing functional [NiFe]-Hydrogenase-2 of Escherichia coli from purified components. The maturation process included formation and insertion of the NiFe(CN)2CO cofactor into the large subunit, endoproteolytic cleavage of the C-terminal extension, and dimerization with the small subunit. Biochemical and spectroscopic analysis indicated that the C-terminal extension of the large subunit is essential for recognition by the maturation machinery. Only upon completion of cofactor insertion removal of the C-terminal extension was observed. Our results indicate that endoproteolytic cleavage is a central checkpoint in the maturation process. Here, cleavage temporally orchestrates cofactor insertion and protein assembly and ensures that only cofactor-containing protein can continue along the assembly line toward functional [NiFe]-hydrogenase.

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Functional Analysis of Human Cytochrome P450 21A2 Variants Involved in Congenital Adrenal Hyperplasia [Molecular Bases of Disease]

Cytochrome P450 (P450, CYP) 21A2 is the major steroid 21-hydroxylase, converting progesterone to 11-deoxycorticosterone and 17α-hydroxy(OH)progesterone to 11-deoxycortisol. More than 100 CYP21A2 variants give rise to congenital adrenal hyperplasia (CAH). We previously reported a structure of wild-type (WT) human P450 21A2 with bound progesterone and now present a structure bound to the other substrate (17α-OH progesterone). We found that the 17α-OH progesterone- and progesterone-bound complex structures are highly similar, with only some minor differences in surface loop regions. Twelve P450 21A2 variants associated with either salt-wasting (SW) or nonclassical (NC) forms of CAH were expressed, purified, and analyzed. The catalytic activities of these 12 variants ranged from 0.00009% to 30% of WT P450 21A2, and the extent of heme incorporation from 10% to 95% of the WT. Substrate dissociation constants (Ks) for four variants were 37-13,000 fold higher than for WT P450 21A2. Cytochrome b5, which augments several P450 activities, inhibited P450 21A2 activity. Similar to the WT enzyme, high noncompetitive intermolecular kinetic deuterium isotope effects (≥ 5.5) were observed for all six P450 21A2 variants examined for 21-hydroxylation of [21-d3]-progesterone, indicating that C-H bond breaking is a rate-limiting step over a 104-fold range of catalytic efficiency. Using UV-visible and CD spectroscopy, we found that P450 21A2 thermal stability assessed in bacterial cells and with purified enzymes differed among SW- and NC-associated variants, but these differences did not correlate with catalytic activity. Our in-depth investigation of CAH-associated P450 21A2 variants reveals critical insight into the effects of disease-causing mutations on this important enzyme.

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Identification of karyopherins involved in the nuclear import of RNA exosome subunit Rrp6 in Saccharomyces cerevisiae [Gene Regulation]

The exosome is a conserved multiprotein complex essential for RNA processing and degradation. The nuclear exosome is a key factor for pre-rRNA processing through the activity of its catalytic subunits, Rrp6 and Rrp44. In Saccharomyces cerevisiae, Rrp6 is exclusively nuclear and has been shown to interact with exosome cofactors. With the aim of analyzing proteins associated with the nuclear exosome, in this work, we purified the complex with Rrp6-TAP, identified the co-purified proteins by mass spectrometry, and found karyopherins to be one of the major groups of proteins enriched in the samples. By investigating the biological importance of these protein interactions, we identified Kap95 and Sxm1 as the most important karyopherins for Rrp6 nuclear import and the nuclear localization signals recognized by them. Based on the results shown here, we propose a model of multiple pathways for the transport of Rrp6 to the nucleus.

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Integrative proteomics and biochemical analyses define Ptc6p as the Saccharomyces cerevisiae pyruvate dehydrogenase phosphatase [Bioenergetics]

The pyruvate dehydrogenase complex (PDC) is the primary metabolic checkpoint connecting glycolysis and mitochondrial oxidative phosphorylation, and is important for maintaining cellular and organismal glucose homeostasis. Phosphorylation of the PDC E1 subunit was identified as a key inhibitory modification in bovine tissue approximately 50 years ago, and this regulatory process is now known to be conserved throughout evolution. Although Saccharomyces cerevisiae is a pervasive model organism for investigating cellular metabolism and its regulation by signaling processes, the phosphatase(s) responsible for activating the PDC in S. cerevisiae has not been conclusively defined. Here, using comparative mitochondrial phosphoproteomics, analyses of protein-protein interactions by affinity enrichment-mass spectrometry, and in vitro biochemistry, we define Ptc6p as the primary PDC phosphatase in S. cerevisiae. Our analyses further suggest additional substrates for related S. cerevisiae phosphatases and describe the overall phosphoproteomic changes that accompany mitochondrial respiratory dysfunction. In summary, our quantitative proteomics and biochemical analyses have identified Ptc6p as the primary-and likely sole-S. cerevisiae PDC phosphatase, closing a key knowledge gap about the regulation of yeast mitochondrial metabolism. Our findings highlight the power of integrative omics and biochemical analyses for annotating the functions of poorly characterized signaling proteins.

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Solution Structure of Domain 1.1 of the {sigma}A Factor from Bacillus subtilis is Preformed for Binding to the RNA Polymerase Core [Enzymology]

Bacterial RNA polymerase (RNAP) requires σ factors to recognize promoter sequences. Domain 1.1 of primary σ factors (σ1.1) prevents their binding to promoter DNA in the absence of RNAP, and when in complex with RNAP, it occupies RNAP's DNA-binding channel. Currently, two 3D structures of σ1.1 are available: from Escherichia coli in complex with RNAP and from Thermotoga maritima solved free in solution. However, these two structures significantly differ, and it is unclear whether this difference is due to an altered conformation upon RNAP binding or to differences in intrinsic properties between the proteins from these two distantly related species. Here, we report the solution structure of σ1.1 from the Gram-positive bacterium Bacillus subtilis. We found that B. subtilis σ1.1 is highly compact because of additional stabilization not present in σ1.1 from the other two species and that it is more similar to E. coli σ1.1. Moreover, modeling studies suggested that \B. subtilis σ1.1 requires minimal conformational changes for accommodating RNAP in the DNA channel, whereas T. maritima σ1.1 must be rearranged to fit therein. Thus, the mesophilic species B. subtilis and E. coli share the same σ1.1 fold, whereas the fold of σ1.1 from the thermophile T. maritima is distinctly different. Finally, we describe an intriguing similarity between σ1.1 and δ, an RNAP-associated protein in B. subtilis, bearing implications for the so far unknown binding site of δ on RNAP. In conclusion, our results shed light on the conformational changes of σ1.1 required for its accommodation within bacterial RNAP.

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A dock and coalesce mechanism driven by hydrophobic interactions governs Cdc42 binding with its effector protein ACK [Protein Structure and Folding]

Cdc42 is a Rho-family small G protein that has been widely studied for its role in controlling the actin cytoskeleton and plays a part in several potentially oncogenic signalling networks. Similar to most other small G proteins, Cdc42 binds to many downstream effector proteins to elicit its cellular effects. These effector proteins all engage the same face of Cdc42, the conformation of which is governed by the activation state of the G protein. Previously, the importance of individual residues in conferring binding affinity has been explored for residues within Cdc42 for three of its CRIB effectors, activated Cdc42 kinase (ACK), p21-activated kinase (PAK), and Wiskott-Aldrich syndrome protein (WASP). Here, in a complementary study, we have used our structure of Cdc42 bound to ACK via an intrinsically disordered ACK region, to guide an analysis of the Cdc42 interface on ACK, creating a panel of mutant proteins with which we can now describe the complete energetic landscape of the Cdc42-binding site on ACK. Our data suggest that the binding affinity of ACK relies on several conserved residues that are critical for stabilizing the quaternary structure. These residues are centred on the CRIB region, with the complete binding region anchored at each end by hydrophobic interactions. These findings suggest that ACK adopts a dock and coalesce binding mechanism with Cdc42. In contrast to other CRIB-family effectors and indeed other intrinsically disordered proteins, hydrophobic residues likely drive Cdc42-ACK binding.

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Synthesis of the Ca2+-mobilizing messengers, NAADP and cADPR, by intracellular CD38 enzyme in mouse heart: role in {beta}-adrenoceptor signaling [Signal Transduction]

Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (cADPR) are Ca2+-mobilizing messengers important for modulating cardiac excitation-contraction coupling and pathophysiology. CD38, which belongs to the ADP-ribosyl cyclase (ARC) family, catalyzes synthesis of both NAADP and cADPR in vitro. However, it remains unclear whether this is the main enzyme for their production under physiological conditions. Here, we show that membrane fractions from WT but not CD38-/- mouse hearts supported NAADP and cADPR synthesis. Membrane permeabilization of cardiac myocytes with saponin and/or Triton X-100 increased NAADP synthesis, indicating that intracellular CD38 contributes to NAADP production. The permeabilization also permitted immunostaining of CD38, with a striated pattern in WT myocytes, while CD38-/- myocytes and non-permeabilized WT myocytes showed little or no staining, without striation. A component of $\beta$-adrenoceptor signaling in the heart involves NAADP and lysosomes. Accordingly, in the presence of isoproterenol, Ca2+ transients and contraction amplitudes were smaller in CD38-/- myocytes than WT. In addition, suppressing lysosomal function with bafilomycin A1 reduced the isoproterenol-induced increase in Ca2+ transients in cardiac myocytes from WT but not CD38-/- mice. Whole hearts isolated fromCD38-/- mice and exposed to isoproterenol showed reduced arrhythmias. SAN4825, an ARC inhibitor, that reduced cADPR and NAADP synthesis in mouse membrane fractions, was shown to bind to CD38 in docking simulations, and reduced the isoproterenol-induced arrhythmias in WT hearts. These observations support generation of NAADP and cADPR by intracellular CD38, which contributes to effects of β-adrenoceptor stimulation (to increase both Ca2+ transients and the tendency to disturb heart rhythm).

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Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy [Research]

We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor-derived cytokines. This stimulates autotaxin (ATX) secretion from adipocytes, whereas breast cancer cells produce insignificant ATX. Lysophosphatidate produced by ATX promotes inflammatory cytokine secretion in a vicious inflammatory cycle, which increases tumor growth and metastasis and decreases response to chemotherapy. We hypothesized that damage to adipose tissue during radiotherapy for breast cancer should promote lysophosphatidic acid (LPA) signaling and further inflammatory signaling, which could potentially protect cancer cells from subsequent fractions of radiation therapy. To test this hypothesis, we exposed rat and human adipose tissue to radiation doses (0.25–5 Gy) that were expected during radiotherapy. This exposure increased mRNA levels for ATX, cyclooxygenase-2, IL-1β, IL-6, IL-10, TNF-α, and LPA1 and LPA2 receptors by 1.8- to 5.1-fold after 4 to 48 h. There were also 1.5- to 2.5-fold increases in the secretion of ATX and 14 inflammatory mediators after irradiating at 1 Gy. Inhibition of the radiation-induced activation of NF-B, cyclooxygenase-2, poly (ADP-ribose) polymerase-1, or ataxia telangiectasia and Rad3-related protein blocked inflammatory responses to -radiation. Consequently, collateral damage to adipose tissue during radiotherapy could establish a comprehensive wound-healing response that involves increased signaling by LPA, cyclooxygenase-2, and other inflammatory mediators that could decrease the efficacy of further radiotherapy or chemotherapy.—Meng, G., Tang, X., Yang, Z., Benesch, M. G. K., Marshall, A., Murray, D., Hemmings, D. G., Wuest, F., McMullen, T. P. W., Brindley, D. N. Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy.

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Vibrational Spectroscopies and Chemometry for Nondestructive Identification and Differentiation of Painting Binders

A comprehensive dataset of vibrational spectra of different natural organic binding media is presented and discussed. The binding media were applied on a glass substrate and analyzed after three months of natural ageing. The combination of Raman and FT-NIR spectroscopies allows for an improved identification of these materials as Raman technique is more informative about the skeletal vibrations, while FT-NIR spectroscopy is more sensitive to the substituents and polar groups. The experimental results are initially discussed in the framework of current spectral assignment. Then, multivariate analysis (PCA) is applied leading to differentiation among the samples. The two major principal components allow for a complete separation of the different classes of organic materials. Further differentiation within the same class is possible thanks to the secondary components. The loadings obtained from PCA are discussed on the basis of the spectral assignment leading to clear understanding of the physical basis of this differentiation process.

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A Quantum-Chemical DFT Approach to Elucidation of the Chirality Transfer Mechanism of the Enantioselective Suzuki–Miyaura Cross-Coupling Reaction

The DFT calculations of the simplified model of the asymmetric Suzuki–Miyaura coupling reaction were performed at the M062x/LANL2DZ theory level at first. It was found that enantioselective reactions mediated by the palladium complexes of chiral C,P-ligands follow a four-stage mechanism similar to that proposed previously as one of the most credible mechanisms. It should be underlined that the presence of substituents in the substrates and the chiral ligand at ortho positions determines the energies of possible diastereoisomeric transition states and intermediates in initial reaction steps. This suggests that, in practice, a sharp selection of theoretically possible paths of chirality transfer from the catalyst to the product should have a place and, therefore, the absolute configuration of the formed atropisomeric product is defined and can be predicted.

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A Swarm Optimization Genetic Algorithm Based on Quantum-Behaved Particle Swarm Optimization

Quantum-behaved particle swarm optimization (QPSO) algorithm is a variant of the traditional particle swarm optimization (PSO). The QPSO that was originally developed for continuous search spaces outperforms the traditional PSO in search ability. This paper analyzes the main factors that impact the search ability of QPSO and converts the particle movement formula to the mutation condition by introducing the rejection region, thus proposing a new binary algorithm, named swarm optimization genetic algorithm (SOGA), because it is more like genetic algorithm (GA) than PSO in form. SOGA has crossover and mutation operator as GA but does not need to set the crossover and mutation probability, so it has fewer parameters to control. The proposed algorithm was tested with several nonlinear high-dimension functions in the binary search space, and the results were compared with those from BPSO, BQPSO, and GA. The experimental results show that SOGA is distinctly superior to the other three algorithms in terms of solution accuracy and convergence.

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Severe Rhabdomyolysis due to Presumed Drug Interactions between Atorvastatin with Amlodipine and Ticagrelor

Atorvastatin and ticagrelor combination is a widely accepted therapy for secondary prevention of ischaemic heart disease. However, rhabdomyolysis is a well-known rare side effect of statins which should be considered when treatments are combined with cytochrome P450 3A4 enzyme inhibitors. We report a case of atorvastatin and ticagrelor associated severe rhabdomyolysis that progressed to multiorgan failure requiring renal replacement therapy, inotropes, intubation, and mechanical ventilation. Despite withdrawal of the precipitating cause and the supportive measures including renal replacement therapy, creatinine kinase increased due to ongoing rhabdomyolysis rapidly progressing to upper and lower limbs weakness. A muscle biopsy was performed to exclude myositis which confirmed extensive myonecrosis, consistent with statin associated rhabdomyolysis. After a prolonged ventilatory course in the intensive care unit, patient’s condition improved with recovery from renal and liver dysfunction. The patient slowly regained her upper and lower limb function; she was successfully weaned off the ventilator and was discharged for rehabilitation. To our knowledge, this is a second case of statin associated rhabdomyolysis due to interaction between atorvastatin and ticagrelor. However, our case differed in that the patient was also on amlodipine, which is considered to be a weak cytochrome P450 3A4 inhibitor and may have further potentiated myotoxicity.

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A Clinical Prospective Observational Cohort Study on the Prevalence and Primary Diagnostic Accuracy of Occult Vertebral Fractures in Aged Women with Acute Lower Back Pain Using Magnetic Resonance Imaging

Background. Elderly female patients complaints of acute low back pain (LBP) may involve vertebral fracture (VF), among which occult VF (OVF: early-stage VF without any morphological change) is often missed to be detected by primary X-ray examination. The current study aimed to investigate the prevalence of VF and OVF and the diagnostic accuracy of the initial X-ray in detecting OVF. Method. Subjects were elderly women (>70 years old) complaining of acute LBP with an accurate onset date. Subjects underwent lumbar X-ray, magnetic resonance imaging (MRI), and bone mineral density (BMD) measurement at their first visit. The distribution of radiological findings from X-ray and magnetic resonance imaging (MRI) as well as the calculation of the prevalence of VF and OVF are investigated. Results. The prevalence of VF among elderly women with LBP was 76.5% and L1 was the most commonly injured level. Among VF cases, the prevalence of OVF was 33.3%. Furthermore, osteoporotic patients tend to show increased prevalence of VF (87.5%). The predictive values in detecting VF on the initial plain X-ray were as follows: sensitivity, 51.3%; specificity, 75.0%; and accuracy rate, 56.7%. Conclusions. Acute LBP patients may suffer vertebral injury with almost no morphologic change in X-ray, which can be detected using MRI.

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Epigenetic and Neural Circuitry Landscape of Psychotherapeutic Interventions

The science behind psychotherapy has garnered considerable interest, as objective measures are being developed to map the patient’s subjective change over the course of treatment. Prenatal and early life influences have a lasting impact on how genes are expressed and the manner in which neural circuits are consolidated. Transgenerationally transmitted epigenetic markers as well as templates of enhanced thought flexibility versus evasion can be passed down from parent to child. This influences gene expression/repression (impacting neuroplasticity) and kindling of neurocircuitry which can perpetuate maladaptive cognitive processing seen in a number of psychiatric conditions. Importantly, genetic factors and the compounding effects of early life adversity do not inexorably lead to certain fated outcomes. The concepts of vulnerability and resilience are becoming more integrated into the framework of “differential susceptibility,” speaking to how corrective environmental factors may promote epigenetic change and reconfigure neural templates, allowing for symptomatic improvement. Psychotherapy is one such factor, and this review will focus on our current knowledge of its epigenetic and neurocircuitry impact.

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Buzzing Wild Bee Visits Enhance Seed Set in Eggplant, Solanum melongena

Sixty percent of the angiosperms with poricidal anthers are buzz-pollinated by bees (Hymenoptera: Apoidea: Apiformes). Plant taxa with Solanum-type flowers have larger anthers and shorter filaments. Solanum melongena (Solanaceae) is more commonly and efficiently pollinated by buzz pollinators. The present study documented bees and their diurnal pattern of visitation to flowers, relationship between their handling time and flower age, and the effect of bee visits on fruit and seed set in S. melongena in two sites in Kandy District. Efficiency of buzz pollination over pollination in the absence of bees was determined using open buds and buds covered with pollinator exclusion bags. On average, 150 days were taken to complete the life cycle of Solanum melongena. Three buzzing bees and two nonbuzzing bees in site I and five buzzing bees and two nonbuzzing bees in site II were recorded. Handling time of Pachynomia sp. and Hoplonomia westwoodi indicates that bees spend more time at new flowers than at old flowers. Handling time is higher in the smaller bee, Pachynomia sp., than in the larger bee, H. westwoodi. Statistical data on pollinator exclusion experiment revealed that the fruit set and seed set of S. melongena are enhanced by buzz-pollinating bees.

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Hydrogen Gas Sensing Using Palladium-Graphene Nanocomposite Material Based on Surface Acoustic Wave

We report the fabrication and characterization of surface acoustic wave (SAW) hydrogen sensors using palladium-graphene (Pd-Gr) nanocomposite as sensing material. The Pd-Gr nanocomposite as sensing layer was deposited onto SAW delay line sensor-based interdigitated electrodes (IDTs)/aluminum nitride (AlN)/silicon (Si) structure. The Pd-Gr nanocomposite was synthesized by a chemical route and deposited onto SAW sensors by air-brush spraying. The SAW H2 sensor using Pd-Gr nanocomposite as a sensing layer shows a frequency shift of 25 kHz in 0.5% H2 concentration at room temperature with good repeatability and stability. Moreover, the sensor showed good linearity and fast response/recovery within ten seconds with various H2 concentrations from 0.25 to 1%. The specific interaction between graphene and SAW transfer inside AlN/Si structures yields a high sensitivity and fast response/recovery of SAW H2 sensor based on Pd-Gr/AlN/Si structure.

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Closer to a Uniform Language in Colposcopy: Study on the Potential Application of 2011 International Federation for Cervical Pathology and Colposcopy Terminology in Clinical Practice

As the newest colposcopic terminology, the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) classification provides standardized interpretation of colposcopic findings. In this study, we analyzed the colposcopic accuracy and the significance of individual findings according to the 2011 IFCPC classification in 525 patients, reviewed by 13 trained colposcopists. Results show that colposcopic diagnoses are in 64.95% perfect agreement with cervical pathology, with 63.64% sensitivity and 96.01% specificity for high-grade squamous intraepithelial lesion (HSIL+). And the accuracy is reproducible across different experienced examiners. Many individual findings, especially the two new signs, inner border sign and ridge sign, are proved to have good predictive accuracy, while iodine negativity demonstrates an inferior performance. However, the distribution of three cervical transformation zone (TZ) types is heterogeneous in examiners. A comparison was also made of the findings of another two colposcopists without nomenclature training according to the Reid Colposcopic Index (RCI), modified RCI, and Swede Score. Results show that colposcopic accuracies in them are lower than in those nomenclature trained colposcopists. The 2011 IFCPC nomenclature improves colposcopic accuracy in trained colposcopists, like speaking the same language. However, the reproducibility of TZ and the predictive value of a few signs remain to be discussed.

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Formation Mechanism and Reduction Technology of Mining-Induced Fissures in Shallow Thick Coal Seam Mining

Surface mining-induced fissures formed in shallow coal seam mining have serious impact on safety mining and water resources protection. This paper proposes a novel approach to study the formation mechanism and dynamic development of surface mining-induced fissures in shallow coal seam mining. This approach combines field tests, theoretical analysis, and numerical simulations based on the geological condition of shallow coal seam mining in Chuancao Gedan Coal Mine. Two typical surface mining-induced fissures, step-type fissures and collapse-type fissures, are generated in shallow coal seam mining. The fissures with large vertical throw or horizontal opening severely impact water resource protection and surface ecological environment. Surface mining-induced fissures are generated periodically and changed dynamically with the advancing of working face. The vertical throw and horizontal opening of surface fissures are changed dynamically with the movement of loading key strata. The movement forms of loading key strata determine the morphological development of surface fissures. Downward sliding movement of broken rocks causes step-type fissures, while downward rotation movement leads to collapse-type fissures. The degree of the downward sliding and rotation of broken rocks determines the vertical throw and horizontal opening of surface fissures. This paper proposes mining technologies to reduce damaging ground fissures in shallow coal seam mining and analyzes their control effects.

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Protective Effect of a Polyherbal Aqueous Extract Comprised of Nigella sativa (Seeds), Hemidesmus indicus (Roots), and Smilax glabra (Rhizome) on Bleomycin Induced Cytogenetic Damage in Human Lymphocytes

This study was carried out to determine the chemoprotective potential of a polyherbal aqueous decoction comprised of Nigella sativa (seeds), Hemidesmus indicus (roots), and Smilax glabra (rhizome) against bleomycin induced cytogenetic damage in human lymphocytes. Isolated peripheral blood lymphocytes (PBLs) were exposed to bleomycin at a dose of 40 µg/mL for 2 hrs in the presence or absence of different doses of the decoction (100, 300, and 600 µg/mL). Modulatory effect of the decoction on bleomycin induced cytogenetic damage was evaluated by (a) degree of chromosomal aberrations (CA), (b) formation of micronuclei (MN), and (c) induction of γH2AX foci in lymphocytes exposed to bleomycin. Lymphocytes pretreated with the decoction showed that a significant reduction () in bleomycin induced (a) stable and unstable chromosome aberrations (CA), (b) MN formation, and (c) formation of H2AX foci, when compared to lymphocytes treated only with bleomycin. The decoction by itself did not induce any significant cytogenetic damage in PBLs. Overall results of the present study confirm that the decoction can attenuate the cytogenetic damage mediated by bleomycin in human PBLs.

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Adenosine Triphosphate Promotes Allergen-Induced Airway Inflammation and Th17 Cell Polarization in Neutrophilic Asthma

Adenosine triphosphate (ATP) is a key mediator to alert the immune dysfunction by acting on P2 receptors. Here, we found that allergen challenge caused an increase of ATP secretion in a murine model of neutrophilic asthma, which correlated well with neutrophil counts and interleukin-17 production. When ATP signaling was blocked by intratracheal administration of the ATP receptor antagonist suramin before challenge, neutrophilic airway inflammation, airway hyperresponsiveness, and Th17-type responses were reduced significantly. Also, neutrophilic inflammation was abrogated when airway ATP levels were locally neutralized using apyrase. Furthermore, ATP promoted the Th17 polarization of splenic CD4+ T cells from DO11.10 mice in vitro. In addition, ovalbumin (OVA) challenge induced neutrophilic inflammation and Th17 polarization in DO11.10 mice, whereas administration of suramin before challenge alleviated these parameters. Thus, ATP may serve as a marker of neutrophilic asthma, and local blockade of ATP signaling might provide an alternative method to prevent Th17-mediated airway inflammation in neutrophilic asthma.

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A Rare Case of Paraneoplastic Aortitis Associated with Chronic Myelomonocytic Leukemia

Aortitis is a broad term describing inflammation of the aorta. The most common causes of aortitis are the large-vessel vasculitides giant cell arteritis and Takayasu arteritis. Other etiologies include aortitis associated with other autoimmune disorders, infectious causes, and paraneoplastic and idiopathic cases. We describe a rare case of a large-vessel arteritis occurring in association with chronic myelomonocytic leukemia (CMML). A 68-year-old female with recent diagnosis of CMML presented to our office for evaluation of abnormal chest computed tomography (CT) that showed inflammation surrounding the entirety of thoracic and abdominal aorta, consistent with aortitis. In the absence of other evident causes of large-vessel vasculitis, we attributed this finding to a paraneoplastic autoimmune phenomenon and started treatment with systemic glucocorticoids. This rare case emphasizes the need to recognize autoimmune complications in CMML and treat the inflammation along with the primary malignancy promptly.

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Management of Severe Developmental Regression in an Autistic Child with a 1q21.3 Microdeletion and Self-Injurious Blindness

We report the case of a young boy with nonverbal autism and intellectual disability, with a rare de novo 1q21.3 microdeletion. The patient had early and extreme self-injurious behaviours that led to blindness, complicated by severe developmental regression. A significant reduction in the self-injurious behaviours and the recovery of developmental dynamics were attained in a multidisciplinary neurodevelopmental inpatient unit. Improvement was obtained after managing all causes of somatic pains, using opiate blockers and stabilizing the patient’s mood. We offered both sensorimotor developmental approach with therapeutic body wrap and specific psychoeducation adapted to his blindness condition for improving his communication abilities.

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Efficient Solutions to Two-Party and Multiparty Millionaires’ Problem

The millionaires’ problem is the basis of secure multiparty computation and has many applications. Using a vectorization method and the Paillier encryption scheme, we first propose a secure two-party solution to the millionaires’ problem, which can determine , or in one execution. Subsequently, using the vectorization and secret splitting methods, we propose an information-theoretically secure protocol to solve the multiparty millionaires’ problem (a.k.a. secure sorting problem), and this protocol can resist collusion attacks. We analyze the accuracy and security of our protocols in the semihonest model and compare the computational and communication complexities between the proposed protocols and the existing ones.

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Mitophagy Transcriptome: Mechanistic Insights into Polyphenol-Mediated Mitophagy

Mitochondria are important bioenergetic and signalling hubs critical for myriad cellular functions and homeostasis. Dysfunction in mitochondria is a central theme in aging and diseases. Mitophagy, a process whereby damaged mitochondria are selectively removed by autophagy, plays a key homeostatic role in mitochondrial quality control. Upregulation of mitophagy has shown to mitigate superfluous mitochondrial accumulation and toxicity to safeguard mitochondrial fitness. Hence, mitophagy is a viable target to promote longevity and prevent age-related pathologies. Current challenge in modulating mitophagy for cellular protection involves identification of physiological ways to activate the pathway. Till date, mitochondrial stress and toxins remain the most potent inducers of mitophagy. Polyphenols have recently been demonstrated to protect mitochondrial health by facilitating mitophagy, thus suggesting the exciting prospect of augmenting mitophagy through dietary intake. In this review, we will first discuss the different surveillance mechanisms responsible for the removal of damaged mitochondrial components, followed by highlighting the transcriptional regulatory mechanisms of mitophagy. Finally, we will review the functional connection between polyphenols and mitophagy and provide insight into the underlying mechanisms that potentially govern polyphenol-induced mitophagy.

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Health Brokers: How Can They Help Deal with the Wickedness of Public Health Problems?

Background. The role of health broker is a relatively new one in public health. Health brokers aim to create support for efforts to optimise health promotion in complex or even “wicked” public health contexts by facilitating intersectoral collaborations and by exchanging knowledge with different stakeholders. The current study aimed to explore the role of health brokers, by examining the motivational, contextual, and behaviour-related factors they have to deal with. Methods. Fifteen professionals from various backgrounds and from various policy and practice organisations were recruited for a semistructured interview. To structure the interviews, we developed the “Health Broker Wheel” (HBW), a framework we then specified with more details derived from the interviews. Results. We identified seven primary types of behaviour that health brokers need to engage in: recognizing opportunities, agenda setting, implementing, network formation, intersectoral collaboration, adaptive managing, and leadership. Determinants of health brokers’ behaviours were identified and categorised as capability, opportunities, motivation, and local or national contextual factors. Conclusion. The health brokers’ role can be seen as an operational approach and is visualised in the HBW. This framework can assist further research to monitor and evaluate this role, and health promotion practitioners can use it as a tool to implement the health brokers’ role and to facilitate intersectoral collaboration.

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CathROB: A Highly Compact and Versatile Remote Catheter Navigation System

Several remote catheter navigation systems have been developed and are now commercially available. However, these systems typically require specialized catheters or equipment, as well as time-consuming operations for the system set-up. In this paper, we present CathROB, a highly compact and versatile robotic system for remote navigation of standard tip-steerable electrophysiology (EP) catheters. Key features of CathROB include an extremely compact design that minimizes encumbrance and time for system set-up in a standard cath lab, a force-sensing mechanism, an intuitive command interface, and functions for automatic catheter navigation and repositioning. We report in vitro and in vivo animal evaluation of CathROB. In vitro results showed good accuracy in remote catheter navigation and automatic repositioning (1.5 ± 0.6 mm for the left-side targets, 1.7 ± 0.4 mm for the right-side targets). Adequate tissue contact was achieved with remote navigation in vivo. There were no adverse events, including absence of cardiac perforation or cardiac damage, indicative of the safety profile of CathROB. Although further preclinical and clinical studies are required, the presented CathROB system seems to be a promising solution for an affordable and easy-to-use remote catheter navigation.

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Excessive gestational weight gain in first trimester is a risk factor for exacerbation of asthma during pregnancy: A prospective study of 1283 pregnancies

Acute exacerbation during pregnancy is the most important risk factor for an unfavorable outcome of pregnancy in women with asthma.

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ETV1-positive cells give rise to BRAFV600E mutant gastrointestinal stromal tumors

Gastrointestinal Stromal Tumor (GIST) is the most common subtype of sarcoma. Despite clinical advances in the treatment of KIT/PDGFRA-mutant GIST, similar progress against KIT/PDGFRA-wild type GIST, including mutant BRAF-driven tumors, have been limited by a lack of model systems. ETV1 is a master regulator in the intestinal cells of Cajal (ICC), thought to be the cells of origin of GIST. Here we present a model in which the ETV1 promoter is used to specifically and inducibly drive Cre recombinase in ICC as a strategy to study GIST pathogenesis. Using a conditional allele for BrafV600E, a mutation observed in clinical cases of GIST, we observed that BrafV600E activation was sufficient to drive ICC hyperplasia but not GIST tumorigenesis. In contrast, combining BrafV600E activation with Trp53 loss was sufficient to drive both ICC hyperplasia and formation of multifocal GIST-like tumors in the mouse GI tract with 100% penetrance. This mouse model of sporadic GIST model was amenable to therapeutic intervention and it recapitulated clinical responses to RAF inhibition seen in human GIST. Our work offers a useful in vivo model of human sporadic forms of BRAF-mutant GIST to help unravel its pathogenesis and therapeutic response to novel experimental agents.

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Meta-Synthesis of Qualitative Research on Facilitators and Barriers of Return to Work After Stroke


Purpose Despite existing rehabilitation services, return to work (RTW) rates among stroke survivors are quite low. An increased number of qualitative studies have been conducted to identify facilitators and barriers to RTW after stroke and to derive recommendations for future interventions. The aim of our study was to carry out a meta-synthesis of those studies and thus strengthen evidence in the field. Methods To identify relevant studies (qualitative studies focusing on RTW after stroke, published in English or German between 2000 and 2015), we conducted a systematic literature search in PubMed, OVID, and Web of Science. After assessing the quality of eligible studies, we synthesized their findings according to meta-ethnographic methodology. Results Fourteen out of 553 studies—three of very high, seven of high, three of medium, and one of low quality—met the inclusion criteria. After the extraction of all first-order concepts and their translation into 64 second-order interpretations, we synthesized the findings by developing a model of RTW factors after stroke. It contains factors related to the person (impairments, coping/adaptation, significance of work/RTW motivation), workplace (job demands/work adaptations, disability management, work climate/social support), and rehabilitation services (availability, accessibility, appropriateness), as well as relevant factors in the interaction of these three stakeholders (work capacity, performance and capability, and initial RTW experiences). Three basic principles—adaptiveness, purposefulness, and cooperativeness—complete the model and led us to its name: the APC model. Conclusions Successful RTW after stroke depends on diverse factors and stakeholders. Rehabilitation strategies have to consider this; otherwise they become RTW barriers themselves.


Vocal Behavior in Environmental Noise: Comparisons Between Work and Leisure Conditions in Women With Work-related Voice Disorders and Matched Controls

This study aimed to assess vocal behavior in women with voice-intensive occupations to investigate differences between patients and controls and between work and leisure conditions with environmental noise level as an experimental factor.

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A Randomized Clinical Trial of a Human Acellular Dermal Matrix Demonstrated Superior Healing Rates for Chronic Diabetic Foot Ulcers over Conventional Care and an Active Acellular Dermal Matrix Comparator


This study compared the efficacy and safety of a human acellular dermal matrix (ADM), D-ADM, with a conventional care arm and an active comparator human ADM arm, GJ-ADM, for the treatment of chronic diabetic foot ulcers. The study design was a prospective, randomized controlled trial that enrolled 168 diabetic foot ulcer subjects in 13 centers across 9 states. Subjects in the ADM arms received one application but could receive one additional application of ADM if deemed necessary. Screen failures and early withdrawals left 53 subjects in the D-ADM arm, 56 in the conventional care arm, and 23 in the GJ-ADM arm (2:2:1 ratio). Subjects were followed through 24 weeks with major endpoints at Weeks 12, 16, and 24. Single application D-ADM subjects showed significantly greater wound closure rates than conventional care at all three endpoints while all applications D-ADM displayed a significantly higher healing rate than conventional care at Week 16 and Week 24. GJ-ADM did not show a significantly greater healing rate over conventional care at any of these time points. A blinded, third party adjudicator analyzed healing at Week 12 and expressed ‘strong' agreement (κ=0.837). Closed ulcers in the single application D-ADM arm remained healed at a significantly greater rate than the conventional care arm at 4 weeks post-termination (100% versus 86.7%; p= 0.0435). There was no significant difference between GJ-ADM and conventional care for healed wounds remaining closed. Single application D-ADM demonstrated significantly greater average percent wound area reduction than conventional care for Weeks 2-24 while single application GJ-ADM showed significantly greater wound area reduction over conventional care for Weeks 4–6, 9, and 11–12. D-ADM demonstrated significantly greater wound healing, larger wound area reduction, and a better capability of keeping healed wounds closed than conventional care in the treatment of chronic DFUs. This article is protected by copyright. All rights reserved.

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In Vitro Skin Expansion: Wound Healing Assessment


For treatments requiring split-thickness skin grafts, it is preferable to mesh the grafts. This reduces the amount of excised skin and covers more wound area. The mesh technique, however, destroys surface continuity, which results in scarring. Strain-based bioreactors, on the other hand, have successfully expanded split-thickness skin grafts in vitro within a 7-day period, increasing graft coverage. After in vitro expansion, the expanded skin grafts were tested in a porcine full-thickness excisional wound model. Expanded graft take rate was 100%. Volumetric, histologic, and mechanical assessments indicated that expanded grafts were comparable to unexpanded grafts (positive control). While there was considerable variation in expansion (31% to -3.1%), this technique has the potential to enhance the coverage area of skin grafts while reducing or eliminating scarring. This article is protected by copyright. All rights reserved.

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Effects of robot-assisted upper limb rehabilitation in stroke patients: a systematic review with meta-analysis


Technology-supported training is emerging as a solution to support therapists in their efforts providing high-intensity, repetitive, and task-specific treatment, in order to enhance the recovery process. The aim of this review is to assess the effectiveness of different robotic devices (end-effector and exoskeleton robots) in comparison with any other type of intervention. Furthermore, we aim to assess whether or not better improvements are obtained in the sub-acute phase after stroke onset than in the chronic phase. A research was conducted in the electronic bibliographic databases Cochrane, MEDLINE, and EMBASE. A total of 17 studies were included: 14 randomized controlled trials, 2 systematic reviews, and one meta-analysis. Fugl-Meyer and modified Ashworth scale were selected to measure primary outcomes, i.e., motor function and muscle tone. Functional independence measure and motor activity log were selected to measure secondary outcomes, i.e., activities of daily living. In comparison with conventional therapy, the robot-assisted rehabilitation is more effective in improving upper limb motor function recovery, especially in chronic stroke patients. No significant improvements are observed in the reduction of muscle tone or daily living activities. The present systematic review shows that the use of robotic devices can positively affect the recovery of arm function in patients with stroke.


The Enigmatic Role of Viruses in Multiple Sclerosis: Molecular Mimicry or Disturbed Immune Surveillance?

Publication date: Available online 23 May 2017
Source:Trends in Immunology
Author(s): Jens Geginat, Moira Paroni, Massimiliano Pagani, Daniela Galimberti, Raffaele De Francesco, Elio Scarpini, Sergio Abrignani
Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability. A disturbed immune surveillance in MS would explain several experimental findings, and has important implications for prognosis and therapy.

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Prurigo pigmentosa nach fettreduzierter Diät, therapiert mit Doxycyclin


Prurigo pigmentosa ist eine seltene entzündliche Erkrankung unklarer Ätiologie, bisher am häufigsten in der ethnischen japanischen Bevölkerung beschrieben. Ätiologie und Pathogenese sind nicht vollständig geklärt. Tetrazykline oder Dapson sind Therapie der Wahl. Ein 17-jähriger Schweizer Patient mit türkischen Eltern präsentierte sich mit juckenden Hautveränderungen an Nacken und Stamm, die nach einer Diät aufgetreten sind. Unter der Therapie mit Doxycyclin während 5 Wochen kam es zur kompletten Abheilung mit einer leichten netzartigen Hyperpigmentierung.


Targeting PP2A and proteasome activity ameliorates features of allergic airway disease in mice



Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed if enhancing PP2A activity with Fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S)), or inhibiting proteasome activity with Bortezomib (BORT) could suppress experimental AAD.


Acute AAD was induced in C57BL/6 mice by intraperitoneal sensitisation with ovalbumin (OVA) in combination with intranasal (i.n) exposure to OVA. Chronic AAD was induced in mice with prolonged i.n exposure to crude house dust mite (HDM) extract. Mice were treated with vehicle, FTY720, AAL(S), BORT or AAL(S)+BORT and hallmark features of AAD assessed.


AAL(S) reduced the severity of acute AAD by suppressing tissue eosinophils and inflammation, mucus secreting cell (MSC) numbers, type-2 associated cytokines (Interleukin (IL)-33, thymic stromal lymphopoietin, IL-5 and IL-13), serum immunoglobulin (Ig)E, and airway hyper-responsiveness (AHR). FTY720 only suppressed tissue inflammation and IgE. BORT reduced bronchoalveolar lavage fluid (BALF) and tissue eosinophils and inflammation, IL-5, IL-13, and AHR. Combined treatment with AAL(S)+BORT had complementary effects and suppressed BALF and tissue eosinophils and inflammation, MSC numbers, reduced the production of type-2 cytokines and AHR. AAL(S), BORT and AAL(S)+BORT also reduced airway remodelling in chronic AAD.


These findings highlight the potential of combination therapies that enhance PP2A and inhibit proteasome activity as novel therapeutic strategies for asthma.

This article is protected by copyright. All rights reserved.

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Molecular characterization of Blastocystis sp. in captive wild animals in Qinling Mountains


Blastocystis is one common protist inhabiting in gastrointestinal tracts of animals and humans. Examining the subtypes has important implications for assessing the zoonotic potential of Blastocystis and intestinal health of hosts. In the present study, a total of 497 fecal samples collected from 37 wild animal species in Qinling Mountains were investigated for the presence and subtypes of Blastocystis. Of them, 200 (40.2%) were positive for Blastocystis and 13 subtypes were found, including eight known subtypes (STs1–3, 5, 10, 12–14) and five possible novel subtypes (temporarily named as STs18–22), with ST10 as the predominate subtype and the subtype ST5 was detected in an ostrich for the first time. These findings indicated the wide distribution and specific subtype characteristics of Blastocystis in wild animals of Qinling Mountains.


Sensor-Based Balance Measures Outperform Modified Balance Error Scoring System in Identifying Acute Concussion


Balance assessment is an integral component of concussion evaluation and management. Although the modified balance error scoring system (mBESS) is the conventional clinical tool, objective metrics derived from wearable inertial sensors during the mBESS may increase sensitivity in detecting subtle balance deficits post-concussion. The aim of this study was to identify which stance condition and postural sway metrics obtained from an inertial sensor placed on the lumbar spine during the mBESS best discriminate athletes with acute concussion. Fifty-two college athletes in the acute phase of concussion and seventy-six controls participated in this study. Inertial sensor-based measures objectively detected group differences in the acutely concussed group of athletes while the clinical mBESS did not (p < 0.001 and p = 0.06, respectively). Mediolateral postural sway during the simplest condition of the mBESS (double stance) best classified those with acute concussion. Inertial sensors provided a sensitive and objective measure of balance in acute concussion. These results may be developed into practical guidelines to improve and simplify postural sway analysis post-concussion.


Can Comprehensive Imaging Analysis with Analytic Morphomics and Geriatric Assessment Predict Serious Complications in Patients Undergoing Pancreatic Surgery?


We aimed to determine whether comprehensive imaging analysis with analytic morphomics (AM) enhances or replaces geriatric assessment (GA) in risk-stratifying pancreatic surgery patients. One hundred thirty-four pancreatic surgery patients were identified from a prospective cohort. Sixty-three patients in the cohort had preoperative CT scans in addition to comprehensive geriatric assessments. CT scans were processed using AM. Associations with National Surgical Quality Improvement Program (NSQIP) serious complications were evaluated using univariate analysis and robust elastic net modeling to obtain AUROC curves by adding AM and GA measures to our previously defined clinical base risk model (age, body mass index, American Society of Anesthesiologists classification, and Charlson comorbidity index). NSQIP serious complications were associated with low psoas Hounsfield units (HUs) (p = 0.002), low-density (0 to 30 HU) psoas area (p = 0.01), visceral fat HU (p ≤ 0.001), visceral fat area (p = 0.009), subcutaneous fat HU (p = 0.023), and total body area (p = 0.012) on univariate analysis. Elastic net models incorporating the base model with geriatric assessment and psoas HU (AUC = 0.751), and AM alone (AUC = 0.739) have greater predictive value than the base model alone (AUC = 0.601). The model utilizing AM and GA in combination had the highest predictive value (AUC = 0.841). When combined, AM and GA improve prediction of NSQIP serious complications compared to either technique alone. The additive nature of these two modalities suggests they likely capture unique aspects of a patient's fitness for surgery.


A Nomogram for Predicting Overall Survival of Gastric Cancer Patients with Insufficient Lymph Nodes Examined


Insufficient number of examined lymph nodes (eLNs) was considered to increase significantly the risk of stage migration in gastric cancer patients. The aim of our study is to establish a nomogram predicting the overall survival (OS) for patients with an insufficient number of eLNs. A total of 872 gastric cancer patients with extended lymphadenectomies were assigned randomly (2:1) to the development cohort and the validation cohort. The nomogram was established based on the Cox regression model using the development cohort. The concordance index (C-index) was used to evaluate the discriminative ability. We also compared our model with two other staging systems. Using multivariate analysis, age, sex, tumor location, depth of invasion, macroscopic type, lymphovascular invasion, the number of eLNs, and metastatic lymph nodes were selected and incorporated into the nomogram. The C-index of the nomogram was 0.742 and 0.743 in development and validation cohorts, respectively, which were significantly superior to the C-indices (range 0.705–0.712, all P < 0.001) of American Joint Committee on Cancer (AJCC) seventh edition and lymph node ratio staging systems in both cohorts. We established a nomogram which could predict accurately OS for gastric cancer patients with insufficient number of eLNs.


Intra-Operative Amylase Concentration in Peri-Pancreatic Fluid Predicts Pancreatic Fistula After Distal Pancreatectomy


Post-operative pancreatic fistula (POPF) is a potentially severe complication following distal pancreatectomy. The aim of this study was to assess the predictive value of intra-operative amylase concentration (IOAC) in peri-pancreatic fluid after distal pancreatectomy for the diagnosis of POPF. Consecutive patients who underwent a distal pancreatectomy between November 2014 and September 2016 were included in the analysis. IOAC was measured, followed by drain fluid analysis for amylase on post-operative days (PODs) 1, 3, and 5. Receiver operator characteristic (ROC) analysis was performed to evaluate the discriminative capacity of IOAC as a predictor of POPF. IOAC was measured after distal pancreatectomy in 26 patients. The IOAC correlated significantly with (i) PODs 1, 3, and 5 drain amylase (p < 0.01); (ii) the development of POPF (p < 0.01); and (iii) the Clavien-Dindo grade of surgical complications (p = 0.02). Eighty-three percent of patients with an IOAC > 1000 experienced a post-operative complication (OR 18.3, 95% CI 2.51–103, p < 0.01). ROC curve analysis confirmed the predictive relationship of IOAC and POPF as an excellent test with an area under the curve of 0.92 (95% CI 0.81–0.99, p < 0.01). Measurement of IOAC allows early and accurate categorization of patients at risk for POPF in distal pancreatectomy.


Glomus Tumor of the Stomach: GI Image


The Impact of Hepaticojejunostomy Leaks After Pancreatoduodenectomy: a Devastating Source of Morbidity and Mortality



Hepaticojejunostomy leaks are less frequent than pancreatic leaks after pancreatoduodenectomy, and the current literature suggests comparable outcomes. The purpose of this study was to determine if the hepaticojejunostomy leak adversely affected patient outcomes.


Consecutive cases of pancreatoduodenectomy (n = 924) were reviewed at a single high-volume institution over an 8-year period (2006–2014).


Pancreaticojejunostomy leaks were identified in 217 (23%) patients and hepaticojejunostomy leaks were identified in 24 patients (3%); combined hepaticojejunostomy/pancreaticojejunostomy leaks were identified in 31 patients (3%). Those with hepaticojejunostomy leaks or combined leaks had a significantly increased risk of morbidity when compared to pancreaticojejunostomy leaks or no leak (54 and 58 vs. 34 and 24%, respectively, p < 0.05). The median length of stay was significantly greater for hepaticojejunostomy leaks or combined leaks when compared to pancreatojejunostomy leaks (17 or 14 vs. 9 days, p = 0.001) and those with no leak (17 or 14 vs. 7 days, p = 0.001). Ninety-day mortality for all patients was 3.6%. Hepaticojejunostomy leaks and combined leaks significantly increased 90-day mortality rate (17 and 32%, respectively, p < 0.05).


Hepaticojejunostomy and combined leaks after pancreatoduodenectomy are rarer than pancreaticojejunostomy leaks; these patients are at a significantly increased risk of major morbidity and mortality.


Peliosis Hepatis Mimicking Malignant Hypervascular Tumors



Peliosis hepatis is an uncommon vascular condition characterized by multiple, randomly distributed, blood-filled, and cyst-like cavities throughout the liver. The unique clinical nature consisting of an asymptomatic, benign, and incidental finding sometimes conceals itself even until autopsy. However, the exact pathomechanism remains as yet unproven.


We encountered the patient with multiple hypervascular masses in the whole liver and investigated the clinicopathological features underlying this condition.


Detailed herein is a case of peliosis hepatis on the basis of our findings. Our patient illustrated a lethal instance which mimicked a malignancy although it is usually an indolent finding.


Peliosis hepatis should always be borne in mind as a differential diagnosis of atypical hypervascular hepatic lesion, especially in patients with clinical conditions described in the text.


Returns to Operating Room After Colon and Rectal Surgery in a Tertiary Care Academic Medical Center: a Valid Measure of Surgical Quality?



Returns to the operating room (ROR) have been suggested as a marker of surgical quality. Increasingly, quality and value metrics are utilized for reimbursement as well as public reporting to inform health care consumers. We sought to understand the etiology of ROR and assess the validity of simple ROR as a quality metric.


This was a single referral center retrospective review of all colon and rectal operations between January 1, 2014 and December 31, 2014. Surgical Systems Nurse + was constructed and validated at our institution for classifying ROR as either an unplanned return to the OR, planned return due to complications, planned staged return, or an unrelated return. The primary outcome was the classification of ROR and total number of ROR within 30 days.


Of the 2389 colorectal patients who underwent surgery between January 1, 2014 and December 31, 2014; 214 returned to the operating room within 30 days (9.0%). Among the 214 patients, there were a total of 232 ROR with an average of 1.1 ROR per patient (range 1–4); 90 (38.8%) were unplanned ROR, 49 (21.1%) were planned returns due to complications, 92 (39.7%) were planned staged returns, and 1 (0.4%) were unrelated ROR. The most common reason for an unplanned ROR was an anastomotic leak (n = 21; 9.1%). Overall, unplanned reoperations were rare events (n = 90/2389; 3.8%), largely comprised of patients experiencing an anastomotic abscess or leak (n=21/2389; 0.9%).


In a high volume and complexity academic colon and rectal surgery practice, RORs within 30 days occurred after 10.4% of cases. Unplanned ROR were relatively rare and most commonly associated with an anastomotic leak. Since the majority of ROR were planned-staged returns, overall rate of ROR should be questioned as a metric of surgical quality. Perhaps, the anastomotic leak rate may be a better metric to monitor for quality improvement efforts.


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