The role of the MTHFR C677T polymorphism in methotrexate-induced toxicity in pediatric osteosarcoma patients

http://ift.tt/2sl4PdB

Merging scleractinian genera: the overwhelming genetic similarity between solitary Desmophyllum and colonial Lophelia

Background: In recent years, several types of molecular markers and new microscale skeletal characters have shown potential as powerful tools for phylogenetic reconstructions and higher-level taxonomy of scleractinian corals. Nonetheless, discrimination of closely related taxa is still highly controversial in scleractinian coral research. Here we used newly sequenced complete mitochondrial genomes and 30 microsatellites to define the genetic divergence between two closely related azooxanthellate taxa of the family Caryophylliidae: solitary Desmophyllum dianthus and colonial Lophelia pertusa. Results: In the mitochondrial control region, an astonishing 99.8 % of nucleotides between L. pertusa and D. dianthus were identical. Variability of the mitochondrial genomes of the two species is represented by only 12 non-synonymous out of 19 total nucleotide substitutions. Microsatellite sequence (37 loci) analysis of L. pertusa and D. dianthus showed genetic similarity is about 97 %. Our results also indicated that L. pertusa and D. dianthus show high skeletal plasticity in corallum shape and similarity in skeletal ontogeny, micromorphological (septal and wall granulations) and microstructural characters (arrangement of rapid accretion deposits, thickening deposits). Conclusions: Molecularly and morphologically, the solitary Desmophyllum and the dendroid Lophelia appear to be significantly more similar to each other than other unambiguous coral genera analysed to date. This consequently leads to ascribe both taxa under the generic name Desmophyllum (priority by date of publication). Findings of this study demonstrate that coloniality may not be a robust taxonomic character in scleractinian corals.

http://ift.tt/2r26919

A high-resolution DEM for the Top-Palaeogene surface of the Belgian Continental Shelf

A 1: 250,000 scale map of the surface of the Top-Palaeogene for the Belgian Continental Shelf was created based on extensive analyses of older and recent geological and geophysical datasets. The Top-Palaeogene surface is an important polygenetic unconformity that truncates older strata of the Palaeogene and to a smaller extent some of Neogene age from the overlying Quaternary deposits. As such it represents the base of the latter. The represented surface has been diachronously shaped and reworked through Late Quaternary times by different geological processes (e.g. fluvial, marine, estuarine, periglacial). Additionally, the offshore surface has been attached to the landward Top-Palaeogene surface and was transformed into a uniform 3D surface allowing new and better interpretations to be used in fundamental and applied research underpinning both scientific purposes (e.g. geology, archaeology, palaeogeography), and commercial applications (e.g. wind farms, aggregate extraction, dredging).

http://ift.tt/2skHclk

Holocene shelf sedimentation patterns off equatorial East Africa constrained by climatic and sea-level changes

Equatorial East Africa experienced significant variations in paleoclimatic and paleoceanographic conditions during the Holocene. These environmental changes influenced sedimentation patterns on the continental shelf. To date, however, little is known about the sediment source, its transport to, and deposition on, the Tanzanian shelf. This paper presents a new high-resolution Holocene sedimentary record off northeast Tanzania (equatorial East Africa) and provides insights into how sedimentation patterns responded to climatic and oceanographic changes during the Holocene. Based on grain-size distribution patterns and mineral assemblages, three types of shelf sediments were identified: Type I (fine-grained terrigenous sediment) is dominated by clay minerals that originated from continental weathering; Type II (coarse-grained terrigenous sediment) is mainly composed of feldspar and quartz, derived from reworking of pre-existing deposits; and Type III (biogenic marine sediment), with low- and high-magnesium calcite, was produced by marine carbonate-secreting organisms. The high input of Type I sediment during the early Holocene (10-8 cal kyr BP) was caused by river mouth bypassing. This supply-dominated regime was controlled by intense river discharge and subsequent resuspension of mud in shelf settings, responding to the humid climate in the hinterland and sea-level rise with low rate off Tanzania. The first occurrence of Type II sediments was around 8 cal kyr BP and dominated when sedimentation rates lowered. This accommodation-dominated regime was caused by shoreface bypassing due to an arid climate and sea-level highstand. Type III sediments increased significantly from the early to late Holocene, resulting from the weakening dilution effect of the terrigenous component. The sedimentation pattern on the Tanzanian shelf shifted from allochthonous to autochthonous sedimentation constrained by climatic changes and relative sea-level fluctuations at the end of the early Holocene. Our results also suggest that, with respect to sea-level rise, high sedimentation rate on the continental shelf could be caused by high terrigenous sediment input as a result of a dynamic interplay between the shelf topography and humid climatic conditions inland. (C) 2015 Elsevier B.V. All rights reserved.

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Welk instrumentarium hebben leerkrachten voorhanden om gedrags- en emotionele problemen bij leerlingen in kaart te brengen?

http://ift.tt/2sl19bw

Post-rift tectonic reactivation and its effect on deep-water deposits in the Qiongdongnan Basin, northwestern South China Sea

The post-rift evolution of extensional basins is traditionally thought to be dominated by thermal subsidence due to cessation of the major fault activity during the post-rift stage. The Qiongdongnan Basin, which is located in the northwestern continental margins of the South China Sea, has exhibited significant deviations from typical post-rift characteristics. In the basin, a distinct tectonic reactivation occurred since the Late Miocene (11.6 Ma). Three notable aspects of the observed tectonic reactivation during the post-rift stage include, (1) pre-existing fault reactivation, (2) multiple large-scale magmatic intrusions, and (3) rapid post-rift subsidence. During this period the basin infill significantly changed in depositional environments shifting rapidly from littoral-neritic to bathyal-abyssal environments since Late Miocene. The pre-existing fault activity along the No. 2 fault of the basin resulted in the formation of initial shelf breaks and led to the development of continental slope. In addition, the pre-existing faults along the Central Depression zone created a small sub-basin with distinctive axial negative topography characteristics formed between structural highs. These geomorphological changes led to the formation of the Central Canyon. Large-scale magmatic intrusions occurred along the fault zone in the Central Depression of the basin during the post-rift stage. Those deviations, as evidenced from pre-existing fault reactivation, magmatic intrusions, and rapid post-rift subsidence in the Qiongdongnan Basin is believed to be related to the Hainan Plume event.

http://ift.tt/2r22ccs

Burnout and resilience in anaesthesia and intensive care medicine

1H022H013J02

http://ift.tt/2rHDJvV

Management of elective laryngectomy

1CO12A013A02

http://ift.tt/2rcldbt

Dermoscopic images of malignant and benign skin lesions

http://sfaki.blogspot.com/2017/06/using-watson-to-diagnose-skin-cancer.html

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

6948891480

alsfakia@gmail.com

Tilt-induced cardio-inhibitory reflex syncope (BIOSync trial) : 12-item questionnaire to distinguish between complete transient loss of consciousness (i.e., syncope) and pre-syncope or other minor symptoms and, additionally, to provide a standardized categorical description of the clinical presentation of syncope including duration, reproducibility with previous episodes, presence of prodromes, presence of witnesses, context, and consequences of the episode.

http://sfaki.blogspot.com/2017/06/12-item-questionnaire-to-distinguish.html

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

6948891480

alsfakia@gmail.com

Hypothyreose nach Hemithyreoidektomie − überraschend häufige Komplikation während der Nachsorge

Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-110856

Hintergrund Hemithyreoidektomie ist eine häufige Behandlung einseitiger Schilddrüsenknoten. Postoperative Hypothyreose ist eine häufig unterschätzte Komplikation. Wir untersuchten Inzidenz, Zeitpunkt, Symptomatik sowie mögliche Risikofaktoren der postoperativen Hypothyreose. Material und Methoden 127 Patienten nach Hemithyreoidektomie wurden mit retrospektiver Datenanalyse sowie strukturierter Befragung der nachbetreuenden Hausärzte und Endokrinologen untersucht. Patienten wurden mit dem postoperativen TSH als hypothyreot (> 4.0 mU/L) oder euthyreot (0.4–4.0 mU/L) klassifiziert. Schilddrüsenhormone wurden nach 4–6 Wochen, 6 Monaten und 1 Jahr gemessen. Ergebnisse 55 Patienten (43 %) entwickelten eine postoperative Hypothyreose und 72 (57%) blieben euthyreot. Die Hypothyreose zeigte sich innerhalb der ersten 2 Monaten bei 39 Patienten (71 %), zwischen 2–6 Monaten bei 13 Patienten (24 %) sowie nach 6–12 Monaten bei 3 Patienten (5 %). 33 Patienten (60 %) waren zum Zeitpunkt der Diagnose asymptomatisch. Nur 16 Patienten (29 %) hatten Symptome. Der präoperative TSH Wert war signifikant höher in der Gruppe der hypothyreoten Patienten (1.64), verglichen mit der euthyreoten Gruppe (1.13, P = 0.0017). Die anderen Variablen wie Alter, Geschlecht und präoperativen Werte von T3, T4, Calcium und PTH zeigten keinen signifikanten Unterschied. Schlussfolgerung Die postoperative Hypothyreose ist eine häufige Komplikation nach Hemithyreoidektomie, welche nicht verpasst werden sollte. Präoperativ erhöhter TSH Wert ist ein Risikofaktor für die postoperative Hypothyreose. Alle Patienten nach Hemithyreoidektomie sollten postoperative TSH Kontrollen nach 4–6 Wochen, 6 Monaten und 12 Monaten haben.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2rHqgnO

Diagnosis and following up of Ménière’s disease using multifrequency tympanometry—Cutoff values and temporal changes in measurements

This study aimed to verify cutoff values for G width (the width of bimodal peaks for the waveform obtained when measuring conductance at 2000Hz) in Japanese individuals diagnosed with Ménière's disease (MD) using multifrequency tympanometry (MFT) and to determine the relationship between the G width and ability to hear low-pitched sounds using measurements over time.

http://ift.tt/2r1jcjq

Monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, benralizumab), IL-13 (lebrikizumab, tralokinumab), IL-4 receptor alpha (dupilumab), Immune globuline E (IgE) (omalizumab), anti-Thymic Stromal Lymphopoitin (TSLP) (tezepelumab) and small molecule therapies such as prostaglandin D2 blockers (fevipiprant, timapiprant). New Anti-Eosinophil Drugs for asthma and COPD

http://sfaki.blogspot.com/2017/06/monoclonal-antibodies-against-il-5-or.html

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

6948891480

alsfakia@gmail.com

Incidence, prevalence, and risk of selected ocular disease in adults with atopic dermatitis

Ocular comorbidities are common in atopic dermatitis (AD) as the result of the disease itself or the use of medication. No large-scale epidemiologic data exist on the prevalence of ocular comorbidities in adults with AD.

http://ift.tt/2s9MDUq

Frequency of and risk factors for tumor upstaging after wide local excision of primary cutaneous melanoma

Detecting a more advanced stage of the primary melanoma after wide local excision and reconstruction can complicate patient counseling about prognosis, management of surgical margins, and indications for sentinel lymph node biopsy.

http://ift.tt/2sJgikB

Histopathologic features of melanoma in difficult-to-diagnose lesions: A case-control study

Dermatopathology is considered the gold standard for melanoma diagnosis, but a subset of cases is difficult to diagnose by histopathology.

http://ift.tt/2sa3Kpg

Healing lotion formula with proven superiority to Rx and therapeutic moisturizing lotions translates into improvements in stratum corneum biology and barrier resilience

Barrier integrity and therefore skin dryness falls along a spectrum—from normal to atopic—based on a number of genetic and environmental factors. The outermost layers of the epidermis (stratum corneum, SC) are key for maintaining skin health and barrier quality. For moderate to severe dry skin, the ideal moisturizer should provide initial and sustained hydration as well as repairing the barrier from within. Barrier resilience is indicated by improved SC parameters on regression. The goals of this research were to compare improvement in hydration from a healing test lotion with a combination of high glycerin, petrolatum, and fatty acid versus Rx and marketed therapeutic lotions and to demonstrate improvement in barrier resilience.

http://ift.tt/2sadzTU

The MO-meatocanalplasty: a modification of the M-meatoplasty to address the superior quadrants and the bony canal

Abstract

The meatoplasty of the external auditory canal is a frequently performed otologic procedure in recurrent otitis externa, eczema or frequent accumulation of cerumen due to a narrow meatus of the external ear canal. Numerous surgical techniques have been described. The M-meatoplasty described by Mirck for addressing the external meatus is widely used. However, this technique does not sufficiently enlarge the external ear canal in all cases. Specifically in patients where the ear canal narrowing is most prominent in the postero- and/or anterosuperior quadrants of the lateral meatus the technique needs some modifications. In these cases, an oblique conversion of the M-meatoplasty, the MO-meatocanalplasty, is useful. In cases where the bony canal is also narrow this modification allows for a bony canalplasty while avoiding a retro-auricular approach. The MO-meatocanalplasty can be used in combination with myringoplasty and tympanoplasty.

http://ift.tt/2rS9m4x

Atypical neurofibromatosis type 1 with unilateral limb hypertrophy mimicking overgrowth syndrome

Summary

Neurofibromatosis type 1 (NF1; OMIM 162200), a dominantly inherited multitumor syndrome, results from mutations in the Neurofibromin 1 (NF1) gene. We present the case of a Hungarian woman with the clinical phenotype of NF1 over her whole body and the clinical features of unilateral overgrowth involving her entire left leg. This unusual phenotype suggested either the atypical form of NF1 or the coexistence of NF1 and overgrowth syndrome. Direct sequencing of the genomic DNA isolated from peripheral blood revealed a novel frameshift mutation (c.5727insT, p.V1909fsX1912) in the NF1 gene. Next-generation sequencing of 50 oncogenes and tumour suppressor genes, performed on the genomic DNAs isolated from tissue samples and peripheral blood, detected only wild-type sequences. Based on these results, we concluded that the patient is affected by an unusual phenotype of NF1, and that the observed unilateral overgrowth of the left leg might be a rare consequence of the identified c.5727insT mutation.

http://ift.tt/2s28kVG

Clinical outcomes in a specialist male genital skin clinic: prospective follow-up of 600 patients

Summary

It is important to assess outcomes for medical interventions in order to focus scarce resources on outcomes with a known positive benefit. An open, observational study was performed to assess the clinical outcomes of 600 male patients with a genital skin problem attending a specialist secondary care dermatology facility. Patients were mainly referred by general practitioners and genitourinary medicine physicians. Outcome was measured at 3 and 6 months, and was determined by clinical examination and assessment of patient symptoms. The mean age of the group was 45.3 years. The commonest diagnoses were lichen sclerosus (30.5%), balanitis (17.3%), eczema (12.8%), lichen planus (7.3%), psoriasis (7.2%) and benign lesions (5.5%). The commonest presenting symptoms were genital rash (43%), genital soreness, pain or burning (17.5%), and penile lesions (15.7%). Lichen sclerosus and all forms of balanitis were more common in uncircumcised patients, whereas lichen planus was more common in circumcised males. Short-term outcome was excellent, with 11.5% of patients being reassured and discharged on their first visit, and after 6 months 58% of all patients were clear and 12% had improved. Only 4.5% reported no improvement in symptoms. Diagnostic biopsy demonstrated malignant or premalignant lesions in nearly a fifth of those having a procedure. Close working with urological and genitourinary medicine colleagues is important to manage the various aspects of male health.

http://ift.tt/2t0hRd4

Sinus hypoplasia in the cystic fibrosis rat resolves in the absence of chronic infection

Background

Sinus hypoplasia is a hallmark characteristic in cystic fibrosis (CF). Chronic rhinosinusitis (CRS) is nearly universal from a young age, impaired sinus development could be secondary to loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or consequences of chronic infection during maturation. The objective of this study was to assess sinus development relative to overall growth in a novel CF animal model.

Methods

Sinus development was evaluated in CFTR^−/− and CFTR^+/+ rats at 3 stages of development: newborn; 3 weeks; and 16 weeks. Microcomputed tomography (microCT) scanning, cultures, and histology were performed. Three-dimensional sinus and skull volumes were quantified.

Results

At birth, sinus volumes were decreased in CFTR^−/− rats compared with wild-type rats (mean ± SEM: 11.3 ± 0.85 mm³ vs 14.5 ± 0.73 mm³; p < 0.05), despite similar weights (8.4 ± 0.46 gm vs 8.3 ± 0.51 gm; p = 0.86). CF rat weights declined by 16 weeks (378.4 ± 10.6 gm vs 447.4 ± 15.9 gm; p < 0.05), sinus volume increased similar to wild-type rats (201.1 ± 3.77 gm vs 203.4 ± 7.13 gm; p = 0.8). The ratio of sinus volume to body weight indicates hypoplasia present at birth (1.37 ± 0.12 vs 1.78 ± 0.11; p < 0.05) and showed an increase compared with CFTR^+/+ animals by 16 weeks (0.53 ± 0.02 vs 0.46 ± 0.02; p < 0.05). Rats did not develop histologic evidence of chronic infection.

Conclusion

CF rat sinuses are smaller at birth, but develop volumes similar to wild-type rats with maturation. This suggests that loss of CFTR may confer sinus hypoplasia at birth, but normal development ensues without chronic sinus infection. ©2017 ARSAAOA, LLC.

http://ift.tt/2rcgXZK

CMV-specific T Cell Monitoring Offers Superior Risk Stratification of CMV-seronegative Kidney Transplant Recipients of a CMV-seropositive Donor.

Background: Detectable CMV-specific T cells in CMV-seronegative kidney transplant recipients (KTRs) have been attributed to an absence of circulating antibodies despite CMV-sensitization. The diagnostic value of CMV-specific T cells, however, needs to be implemented in risk stratification for CMV-replication. Methods: 326 KTRs were studied and classified with respect to CMV-serostatus and presence of CMV-specific T cells. Samples were collected pretransplantation, at +1, +2, and +3 months posttransplantation. CMV-specific T cells directed to CMV-IE1 and CMV-pp65 were measured by interferon-[gamma] Elispot assay. Results: 19/67 D+R- KTRs (28%) showed pretransplant CMV-specific T cells. Although no differences were observed for CMV-replication, KTRs with CMV-specific T cells presented with lower initial and peak CMV-loads (p

http://ift.tt/2t0bZ3o

Blockade of HLA Antibody-Triggered Classical Complement Activation in Sera from Subjects Dosed with the Anti-C1s Monoclonal Antibody TNT009 - Results from a Randomized First-in-Human Phase 1 Trial.

Background: Complement may play a key role in antibody-mediated rejection (ABMR). A promising therapeutic approach may be classical pathway (CP) inhibition at the level of early component C1. Methods: In this first-in-human, double-blind, randomized placebo-controlled phase 1 trial, we evaluated the safety and complement inhibitory effect of TNT009, a humanized monoclonal anti-C1s antibody. Sixty-four adult healthy volunteers received either single (n=48; 7 consecutive cohorts: 0.3-100 mg/kg) or 4 weekly infusions (n=16; 2 consecutive cohorts: 30 and 60 mg/kg per infusion) of TNT009 or placebo. To assess the effect of treatment on complement activity, sera from dosed subjects were analysed in a CP activation assay evaluating C3d deposition on HLA-coated microbeads spiked with alloantibodies. Results: Single doses of TNT009 at 3-100 mg/kg uniformly and profoundly inhibited HLA antibody-mediated C3d deposition (>=86% after 60 min), whereby the duration of CP inhibition (2-14 days) was dose-dependent. Four weekly doses persistently blocked complement for 5-6 weeks. Ex vivo serum CP activity was profoundly inhibited when TNT009 concentrations exceeded 20 [mu]g/mL. Infusions were well tolerated without serious or severe adverse events. Conclusions: Treatment with TNT009 was safe and potently inhibited CP activity. Future studies in patients are required to assess the potential of TNT009 for preventing or treating ABMR. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2s2feub

DHRS9 is a Stable Marker of Human Regulatory Macrophages.

Background: The human regulatory macrophage (Mreg) has emerged as a promising cell type for use as a cell-based adjunct immunosuppressive therapy in solid organ transplant recipients. In this brief report, dehydrogenase/reductase 9 (DHRS9) is identified as a robust marker of human Mregs. Materials and Methods: The cognate antigen of a mouse monoclonal antibody raised against human Mregs was identified as DHRS9 by immunoprecipitation and MALDI-MS sequencing. Expression of DHRS9 within a panel of monocyte-derived macrophages was investigated by quantitative PCR, immunoblotting and flow cytometry. Results: DHRS9 expression discriminated human Mregs from a panel of in vitro derived macrophages in other polarisation states. Likewise, DHRS9 expression distinguished Mregs from a variety of human monocyte-derived tolerogenic antigen-presenting cells in current development as cell-based immunotherapies, including Tol-DC, Rapa-DC, DC-10 and PGE2-induced MDSC. A subpopulation of DHRS9-expressing human splenic macrophages was identified by immunohistochemistry. Expression of DHRS9 was acquired gradually during in vitro development of human Mregs from CD14+ monocytes and was further enhanced by IFN-[gamma] treatment on day 6 of culture. Stimulating Mregs with 100 ng/ml lipopolysaccharide for 24-hours did not extinguish DHRS9 expression. Dhrs9 was not an informative marker of mouse Mregs. Conclusion: DHRS9 is a specific and stable marker of human Mregs. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2t0iLq0

Inhibition of spleen tyrosine kinase reduces renal allograft injury in a rat model of acute antibody-mediated rejection in sensitized recipients.

Background: Organ transplantation into sensitized patients with preexisting donor-specific antibodies (DSA) is very challenging. Spleen tyrosine kinase (Syk) promotes leukocyte recruitment and activation via signalling through various cell surface receptors. We investigated whether a selective Syk inhibitor (GS-492429) could suppress antibody-mediated rejection (AMR) in a rat model of AMR in sensitized recipients. Methods: Recipient Lewis rats (RT1l) were immunized with donor (Dark Agouti, RT1av1) spleen cells (day -5). Recipients underwent bilateral nephrectomy and orthotopic renal transplantation (day 0). Cellular rejection was minimized by tacrolimus treatment from day -1. Groups received GS-492429 (30mg/kg/bid) (n=11) or vehicle (n=12) from 1hr before transplantation until being killed on day 3. Results: Vehicle treated recipients developed graft dysfunction on day 1 which rapidly worsened by day 3. Histology showed severe damage (thrombosis, acute tubular injury, capillaritis) and infiltration of many Syk+ leukocytes. GS-492429 did not affect graft dysfunction on day 1, but treatment reduced allograft damage and prevented the rapid deterioration of graft function on day 3. GS-492429 reduced the prominent macrophage infiltrate and reduced the M1 proinflammatory response. Neutrophil and NK cell infiltration and capillary thrombosis were also significantly reduced by GS-492429 treatment. Serum DSA levels and the deposition of IgG and C4d in the allograft were equivalent in the 2 groups. Conclusion: Treatment with a Syk inhibitor significantly reduced renal allograft injury in a model of severe antibody-mediated damage in highly sensitized recipients. Further studies are warranted to determine whether Syk inhibition is a potential adjunctive treatment in clinical AMR. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2s210cE

Reduction in all-cause otitis media-related outpatient visits in children after PCV10 introduction in Brazil

by Ana L. Sartori, Ruth Minamisava, Ana L. Bierrenbach, Cristiana M. Toscano, Eliane T. Afonso, Otaliba L. Morais-Neto, José L. F. Antunes, Elier B. Cristo, Ana Lucia Andrade

Few studies have reported the effect of 10-valent pneumococcal conjugate vaccine (PCV10) on otitis media (OM) in infants. In particular, no population-based study in upper-middle income countries is available. In 2010, Brazil introduced PCV10 into its routine National Immunization Program using a 3+1 schedule. We measured the impact of PCV10 on all-cause OM in children. An interrupted time-series analysis was conducted in Goiânia/Brazil considering monthly rates (per 100,000) of all-cause OM outpatient visits in children aged 2–23 months. We used case-based data from the Outpatient Visits Information System of the Unified Health System coded for ICD-10 diagnosis for the period of August/2008 to July/2015. As a comparator, we used rates of outpatient visits due to all-other causes. The relative reduction of all-cause OM and all-other causes of outpatient visits were calculated as the difference between the predicted and observed cumulative rates of the PCV10 post-vaccination period. We then subtracted the relative reduction of all-other causes of outpatient visits from all-cause OM to obtain the impact of PCV10 on OM. In total, 6,401 OM outpatient visits were recorded in 4,793 children aged 2–23 months. Of these, 922 (19.2%) children had more than one OM episode. A significant reduction in all-cause OM visits was observed (50.7%; 95%CI: 42.2–59.2%; p = 0.013), while the reduction in visits due to all-other causes was 7.7% (95% CI 0.8–14.7%; p

http://ift.tt/2rQvjRk

Biocontrol of the toxigenic plant pathogen Fusarium culmorum by soil fauna in an agroecosystem

Abstract

In 2011 and 2013, a field experiment was conducted in a winter wheat field at Adenstedt (northern Germany) to investigate biocontrol and interaction effects of important members of the soil food web (Lumbricus terrestris, Annelida; Folsomia candida, Collembola and Aphelenchoides saprophilus, Nematoda) on the phytopathogenic fungus Fusarium culmorum in wheat straw. Therefore, soil fauna was introduced in mesocosms in defined numbers and combinations and exposed to either Fusarium-infected or non-infected wheat straw. L. terrestris was introduced in all faunal treatments and combined either with F. candida or A. saprophilus or both. Mesocosms filled with a Luvisol soil, a cover of different types of wheat straw and respective combinations of faunal species were established outdoors in the topsoil of a winter wheat field after harvest of the crop. After a time span of 4 and 8 weeks, the degree of wheat straw coverage of mesocosms was quantified to assess its attractiveness for the soil fauna. The content of Fusarium biomass in residual wheat straw and soil was determined using a double-antibody sandwich (DAS)-ELISA method. In both experimental years, the infected wheat straw was incorporated more efficiently into the soil than the non-infected control straw due to the presence of L. terrestris in all faunal treatments than the non-infected control straw. In addition, Fusarium biomass was reduced significantly in all treatments after 4 weeks (2011: 95–99%; 2013:15–54%), whereupon the decline of fungal biomass was higher in faunal treatments than in non-faunal treatments and differed significantly from them. In 2011, Fusarium biomass of the faunal treatments was below the quantification limit after 8 weeks. In 2013, a decline of Fusarium biomass was observed, but the highest content of Fusarium biomass was still found in the non-faunal treatments after 8 weeks. In the soil of all treatments, Fusarium biomass was below the quantification limit. The earthworm species L. terrestris revealed a considerable potential as an effective biocontrol agent contributing to a sustainable control of a Fusarium plant pathogen in wheat straw, thus reducing the infection risk for specific plant diseases in arable fields.

http://ift.tt/2s97eZ1

Congenital nasal obstruction in infants: A retrospective study and literature review

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Vijay A. Patel, Michele M. Carr
ObjectivesTo identify etiologies of congenital nasal obstruction and describe clinical practice patterns in the evaluation, diagnosis, and treatment of symptomatic infants.MethodsAn electronic chart review from 1/1/2006–10/1/2016 for all patients with a diagnosis of nasal obstruction within the first six months of life using ICD-9 and 10 codes 478.19 and J34.89.ResultsA total of 34 patients were evaluated by the Division of Otolaryngology for this chief complaint. 38% of neonates were born premature and 32% were admitted to the NICU at birth, with a female-to-male ratio of 1:1.4. Presenting signs and symptoms included: stertor (44%), cyanosis (24%), stridor (24%), retractions (21%), rhinorrhea (21%), apnea (12%), and epistaxis (8%). 47% of patients received ancillary radiographic imaging (CT or MRI). Diagnoses observed include: midnasal stenosis (38%), pyriform aperture stenosis (21%), choanal stenosis (12%), dacryocystocele (6%), microrhinia (6%), septal deviation (6%), nasopharyngeal reflux (3%), nasopharyngeal teratoma (3%), neonatal rhinitis (3%), and pharyngeal wall collapse (3%). 71% of patients were noted to have bilateral nasal obstruction. 41% of infants were found to have an associated ear, nose, and throat anomaly. 15% of patients required surgical intervention. The mean time-to-resolution was 240 days.ConclusionCongenital nasal obstruction has a broad differential diagnosis: the timing, onset, and laterality of symptoms can provide insights into the source of upper airway compromise. Most infants improve through conservative management (i.e. suctioning, humidification) and medical therapies (i.e. intranasal drops, nasal sprays).



http://ift.tt/2rRIh1e

Visual cortex activation decrement following cochlear implantation in prelingual deafened children

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Jiahao Liu, Maojin Liang, Yuebo Chen, Yajing Wang, Yuexin Cai, Suijun Chen, Ling Chen, Xianghui Li, Zeheng Qiu, Jiajia Jiang, Junbo Wang, Yiqing Zheng
ObjectiveVisual take-over of the auditory cortex in prelingual deaf children has been widely reported. However, there have been few studies on visual cortex plasticity after cochlear implantation (CI). In this study, we investigated the hypothesis that extrinsic auditory stimulation following CI in prelingual deafened children can induce visual cortex plasticity.MethodVisual evoked potentials (VEPs) were recorded in 37 CI children (4 groups with different use times) and 8 control subjects, in response to sound and nonsound stimuli. Latency and amplitude were analyzed for the P1, N1 and P2 components on the Oz electrode. Comparisons of VEP were conducted between the sound and nonsound stimuli and among different groups in order to view evidence of visual cortex reorganization.ResultsThe latency of the P2 component was significantly longer at the occipital site (Oz) in CI 0M than those in the other four groups. After the effect of age was excluded, a significant negative correlation was found between CI usage and P2 latency of nonsound stimuli. Occipital P1N1 latency and P1 amplitude were not affected by group or stimulus category. However, the N1 and P2 amplitudes were significantly larger in response to a sound stimulus than to a nonsound stimulus.ConclusionOur findings suggest that P2 latency develops with CI usage and may be a biomarker of visual cortex plasticity.



http://ift.tt/2r7wleC

Genetic Variants in the IL-4/IL-13 Pathway Influence Measles Vaccine Responses and Vaccine Failure in Children from Mozambique

Viral Immunology , Vol. 0, No. 0.


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Sending Your Child to Sleep Away Camp With Seasonal or Food Allergies

 

Worried about sending your child to sleep away camp with seasons or food allergies? Lila Kertz, RN, is back on this episode of MomDocs to discuss how to prepare and plan for this summer.

The post Sending Your Child to Sleep Away Camp With Seasonal or Food Allergies appeared first on ChildrensMD.

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Exaggerated T Follicular Helper Cell Responses in LRBA Deficiency Due to Failure of CTLA4-Mediated Regulation

Publication date: Available online 7 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Fayhan J. Alroqi, Louis-Marie Charbonnier, Safa Baris, Ayca Kiykim, Janet Chou, Craig D. Platt, Abdulrahman Algassim, Sevgi Keles, Bandar K. Al Saud, Fowzan S. Alkuraya, Michael Jordan, Raif S. Geha, Talal A. Chatila
PurposeLRBA (lipopolysaccharide-responsive beige like anchor protein) and CTLA4 (cytotoxic T lymphocyte antigen 4) deficiencies give rise to overlapping phenotypes of immune dysregulation and autoimmunity, with dramatically increased frequencies of circulating T Follicular helper (cTFH) cells. We sought to determine the mechanisms of cTFH cell dysregulation in LRBA deficiency and the utility of monitoring cTFH cells as a correlate of clinical response to CTLA4-Ig therapy.MethodscTFH cells and other lymphocyte subpopulations were characterized. Functional analyses included in vitro TFH cell differentiation and cTFH/naïve B cell co-cultures. Serum soluble IL-2 receptor alpha chain (sIL-2Rα), and in vitro immunoglobulin production by cultured B cells were quantified by ELISA.ResultscTFH cell frequencies in patients with LRBA or CTLA4 deficiency sharply declined with CTLA4-Ig therapy, in parallel with other markers of immune dysregulation including sIL-2Rα, CD45RO⁺CD4⁺ effector T cells and auto-antibodies, and predictive of favorable clinical responses. cTFH cells in patients with LRBA deficiency were biased towards a TH1-like cell phenotype, which was partially reversed by CTLA4-Ig therapy. LRBA-sufficient but not -deficient regulatory T (Treg) cells suppressed in vitro TFH cell differentiation in a CTLA4-dependent manner. LRBA deficient TFH cells supported in vitro antibody production by naïve LRBA-sufficient B cells.ConclusionscTFH cell dysregulation in LRBA deficiency reflects impaired control of TFH differentiation due to profoundly decreased CTLA4 expression on Treg cells, and probably contributes to autoimmunity in this disease. Serial monitoring of cTFH cell frequencies is highly useful in gauging the clinical response of LRBA deficient patients to CTLA4-Ig therapy.

Teaser

LRBA and CTLA4 deficiencies are associated with dysregulated TFH cell responses, which may contribute to autoimmunity in these disorders. Monitoring circulating TFH cells may help gauge response to therapy.


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Flow cytometric measurement of STAT1 and STAT3 phosphorylation in CD4+ and CD8+ T cells - Clinical applications in PID diagnostics

Publication date: Available online 7 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Michael Bitar, Andreas Boldt, Stefanie Binder, Michael Borte, Karim Kentouche, Stephan Borte, Ulrich Sack

Teaser

Flow cytometry-based pSTAT1 and pSTAT3 profiling is an effective diagnostic tool to identify PID patients with aberrations in the STAT1 or STAT3 gene.


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Prenatal, intrapartum, and postnatal factors are associated with pediatric eosinophilic esophagitis

Publication date: Available online 7 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Elizabeth T. Jensen, Jonathan T. Kuhl, Lisa J. Martin, Marc E. Rothenberg, Evan S. Dellon
BackgroundMultiple lines of evidence point to the potential importance of early-life environmental factors in the rapid rise in incidence of eosinophilic esophagitis (EoE), but potential exposures have not been extensively studied.ObjectiveTo assess the association between prenatal, intrapartum, and postnatal factors and the development of pediatric EoE using a case-control study.MethodsCases of EoE were recruited from an existing registry at Cincinnati Children's Hospital Medical Center (CCHMC). Population-based community controls were identified from a separate CCHMC registry. Mothers of study subjects were contacted and completed a web-based questionnaire. Crude and adjusted models were used to estimate associations.ResultsMothers of 127 cases and 121 controls were included. We observed a positive association between several early-life factors and EoE, including prenatal (maternal fever: aOR 3.18; 95% CI 1.27, 7.98; preterm labor: aOR 2.18; 95% CI 1.06, 4.48), intrapartum (Cesarean delivery: aOR 1.77; 95% CI 1.01, 3.09) and infancy factors (antibiotic use: aOR 2.30; 95% CI 1.21, 4.38; use of an acid-suppressant: aOR 6.05; 95% CI 2.55, 14.40). We observed an inverse association between having a furry pet in infancy and EoE (aOR 0.58; 95% CI 0.34, 0.97). No associations were observed for breastfeeding or maternal multivitamin or folic acid supplement use.ConclusionEarly-life factors including maternal fever, preterm labor, Cesarean delivery, and antibiotic or acid suppressant use in infancy were associated with risk of pediatric EoE; having a pet in the home was protective. These results add to growing evidence that implicate early-life exposures in EoE pathogenesis.

Teaser

Heritability estimates for EoE suggest that both genetics and early-life environmental factors contribute to disease pathogenesis. The present study identifies several prenatal, intrapartum, and postnatal factors associated with EoE susceptibility.


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Nitric oxide induces human CLA+CD25+Foxp3+ regulatory T cells with skin homing potential

Publication date: Available online 7 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Cunjing Yu, Amanda Fitzpatrick, Duanduan Cong, Chengcan Yao, Jinah Yoo, Andrew Turnbull, Jürgen Schwarze, Mary Norval, Sarah E.M. Howie, Richard B. Weller, Anne L. Astier
Phototherapy releases nitric oxide and can reduce symptoms in Atopic Dermatitis (AD). Nitric oxide induced suppressive regulatory T cells and, post-phototherapy, a clinical improvement in AD correlated with an increased ratio of Tregulatory:Teffector cells.



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Hematopoietic stem cell transplantation in patients with Gain of Function STAT1 Mutation

Publication date: Available online 7 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Jennifer W. Leiding, Satoshi Okada, David Hagin, Mario Abinun, Anna Shcherbina, Dmitry N. Balashov, Vy H.D. Kim, Adi Ovadia, Stephen L. Guthery, Michael Pulsipher, Desa Lilic, Lisa A. Devlin, Sharon Christie, Mark Depner, Sebastian Fuchs, Annet van Royen-Kerkhof, Caroline Lindemans, Aleksandra Petrovic, Kathleen E. Sullivan, Nancy Bunin, Sara Sebnem Kilic, Fikret Arpaci, Oscar de la Calle-Martin, Laura Martinez-Martinez, Juan Carlos Aldave, Masao Kobayashi, Teppei Ohkawa, Kohsuke Imai, Akihiro Iguchi, Chaim M. Roifman, Andrew R. Gennery, Mary Slatter, Hans D. Ochs, Tomohiro Morio, Troy R. Torgerson
BackgroundGain of function mutations in signal transducer and activator of transcription 1 (GOF-STAT1) cause a susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life threatening. Hematopoietic stem cell transplantation (HSCT) has been utilized in some patients with more severe symptoms to treat and cure the disorder. The outcome of HSCT for this disorder is, however, not well established.ObjectiveTo aggregate the worldwide experience of HSCT in GOF-STAT1 patients and to assess outcomes including donor engraftment, overall survival, graft versus host disease, and transplant related complications.MethodsData were collected from an international cohort of 15 GOF-STAT1 patients that had undergone HSCT using a variety of conditioning regimens and donor sources. Retrospective data collection allowed the outcome of transplantation to be assessed. In vitro functional testing was performed to confirm that each of the identified STAT1 variants was, in-fact, a gain of function mutation.ResultsPrimary donor engraftment in this cohort of 15 GOF-STAT1 patients was 74% and overall survival was only 40%. Secondary graft failure was common (50%) and post-transplant event free survival was poor (10% by 100 days). A subset of patients developed hemophagocytic lymphohistiocytosis (HLH) prior to their transplant, contributing to their poor outcomes.ConclusionOur data indicate that HSCT for patients with GOF-STAT1 mutations is curative but has significant risk of secondary graft failure and death.

Teaser

Hematopoietic stem cell transplantation (HSCT) in GOF-STAT1 patients can be curative. HSCT in this cohort is however associated with a relatively high rate of graft failure and other complications that lead to decreased overall survival.


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Mutation of Angiopoietin-1 Gene Associates with a New Type of Hereditary Angioedema

Publication date: Available online 8 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Valeria Bafunno, Davide Firinu, Maria D'Apolito, Giorgia Cordisco, Stefania Loffredo, Angelica Leccese, Maria Bova, Maria Pina Barca, Rosa Santacroce, Marco Cicardi, Stefano Del Giacco, Maurizio Margaglione.
BackgroundHereditary angioedema (HAE) is a rare genetic disease usually due to mutation within the C1 inhibitor or the coagulation Factor XII gene. However, in a series of patients with HAE no causative variants have been described and the pathophysiology of the disease remains unknown (U-HAE). Identification of causative genes in U-HAE is valuable for understanding the cause of the disease.ObjectiveWe conducted genetic studies in Italian patients with U-HAE to identify novel causative genes.MethodsAmong patients belonging to 10 independent families and unrelated index patients with U-HAE disease recruited from the Italian network for C1-INH-HAE (ITACA), we selected a large multiplex family with U-HAE and performed whole-exome sequencing. The angiopoietin-1 gene (ANGPT1) was investigated in all patients with familial or sporadic U-HAE. The effect of ANGPT1 variants was investigated by in silico prediction and using patients and control plasmas and transfected cells.ResultsWe identified a missense mutation (ANGPT1, c.807G>T, p.A119S) in a family with U-HAE. The ANGPT1 p.A119S variant was detected in all members of the index family with U-HAE but not in asymptomatic family members, nor in an additional 20 patients with familial U-HAE, 22 patients with sporadic U-HAE, and 200 controls. Protein analysis of the plasma of patients revealed a reduction of multimeric forms and a reduced ability to bind the natural receptor "tunica interna endothelial cell kinase-2" (TIE2) of the ANGPT1 p.A119S variant. The recombinant mutated ANGPT1 p.A119S formed a reduced amount of multimers and showed a reduced binding capability to its receptor.ConclusionANGPT1 impairment is associated with angioedema and ANGPT1 variants can be the basis of HAE.

Graphical abstract

Teaser

A missense variant in the angiopoietin-1 gene (ANGPT1) represents a novel and independent mechanism leading to vascular permeability and angioedema. Impairment of the endothelial ANGPT1-TIE2 ligand-receptor system may be involved in the pathophysiology of HAE.


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Increased IL-13 expression is independently associated with neo-osteogenesis in chronic rhinosinusitis

Publication date: Available online 7 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Sakiko Oue, Mahnaz Ramezanpour, Sathish Paramasivan, Dijana Miljkovic, Clare M. Cooksley, Ahmed Bassiouni, Judy Ou, Alkis J. Psaltis, Peter-John Wormald, Sarah Vreugde

Teaser

Capsule Summary: Increased expression of IL-13 is independently affected by the neo-osteogenesis state in CRS. IL-13 protein increased osteoblastic bone mineralization in vitro. Our findings indicate that IL-13 may contribute to pathological bone remodelling in recalcitrant CRS.


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B cells control maternofetal priming of allergy and tolerance in a murine model of allergic airway inflammation

Publication date: Available online 7 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Christine Happle, Adan Chari Jirmo, Almut Meyer-Bahlburg, Anika Habener, Heinz Gerd Hoymann, Christian Hennig, Jelena Skuljec, Gesine Hansen
BackgroundAllergic asthma is a chronic lung disease resulting from inappropriate immune responses to environmental antigens. Early tolerance induction is an attractive approach for primary prevention of asthma.ObjectiveWe analysed the mechanisms of perinatal tolerance induction to allergens with particular focus on the role of B cells in preconceptional and early intrauterine immune priming.MethodsWild type (WT) and B cell deficient mice received ovalbumin (OVA) intranasally before mating. Their offspring was analysed in a murine model of allergic airway inflammation.ResultsWhile antigen application before conception protected WT progeny from allergy, it aggravated allergic airway inflammation in B cell deficient offspring. B cell transfer restored protection, demonstrating the crucial role of B cells in perinatal tolerance induction. Effective diaplacentar allergen transfer was detectable in pregnant WT mice but not in pregnant B cell KO dams, and antigen concentrations in WT amniotic fluid were higher than in IgG-free amniotic fluid of B cell deficient dams. Application of OVA/IgG immune complexes (IC) during pregnancy boosted OVA uptake by fetal dendritic cells (DCs). Fetal DCs in humans and mice expressed strikingly higher levels of Fcγ receptors compared to DCs from adults and were highly efficient in taking up OVA-IC. Moreover, murine fetal DCs effectively primed antigen-specific foxp3⁺ Tregs after in vitro coincubation with OVA/IgG containing amniotic fluid.ConclusionOur data support a decisive role for B cells and immunoglobulins during in utero tolerance priming. These findings improve the understanding of perinatal immunity and may support the development of effective primary prevention strategies for allergy and asthma in the future.

Teaser

Maternal allergen application before conception protects murine WT-offspring from allergy but aggravates allergic airway inflammation in B-cell deficient pups. Perinatal tolerance induction is associated with intrauterine antigen/IgG-transfer to fetal DCs which in turn effectively prime antigen-specific Tregs.


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Study Adds Evidence That Flaws in a Tumor's Genetic Mending Kit Drive Treatment Response to Immunotherapy Drugs

In an expanded, three-year clinical trial of 86 patients with colorectal and 11 other kinds of cancer that have so-called 'mismatch repair' genetic defects, scientists at Johns Hopkins Medicine and its Bloomberg~Kimmel Institute for Cancer Immunotherapy have found that half of the patients respond to an immunotherapy drug called pembrolizumab (Keytruda). In a report on the findings, which led the U.S. Food and Drug Administration to approve expanded use of pembrolizumab for patients, the researchers also say they found evidence that the immune responses closely aligned with mutations found in their cancers. The report is published online in the June 8 issue of the journal Science.

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C1q: A fresh look upon an old molecule

Publication date: Available online 7 June 2017
Source:Molecular Immunology
Author(s): Nicole M. Thielens, Francesco Tedesco, Suzanne S. Bohlson, Christine Gaboriaud, Andrea J. Tenner
Originally discovered as part of C1, the initiation component of the classical complement pathway, it is now appreciated that C1q regulates a variety of cellular processes independent of complement activation. C1q is a complex glycoprotein assembled from 18 polypeptide chains, with a C-terminal globular head region that mediates recognition of diverse molecular structures, and an N-terminal collagen-like tail that mediates immune effector mechanisms. C1q mediates a variety of immunoregulatory functions considered important in the prevention of autoimmunity such as the enhancement of phagocytosis, regulation of cytokine production by antigen presenting cells, and subsequent alteration in T-lymphocyte maturation. Furthermore, recent advances indicate additional roles for C1q in diverse physiologic and pathologic processes including pregnancy, tissue repair, and cancer. Finally, C1q is emerging as a critical component of neuronal network refinement and homeostatic regulation within the central nervous system. This review summarizes the classical functions of C1q and reviews novel discoveries within the field.



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Intracellular complement − the complosome − in immune cell regulation

Publication date: Available online 7 June 2017
Source:Molecular Immunology
Author(s): Giuseppina Arbore, Claudia Kemper, Martin Kolev
The complement system was defined over a century ago based on its ability to "complement" the antibody-mediated and cell-mediated immune responses against pathogens. Today our understanding of this ancient part of innate immunity has changed substantially and we know now that complement plays an undisputed pivotal role in the regulation of both innate and adaptive immunity. The complement system consists of over 50 blood-circulating, cell-surface expressed and intracellular proteins. It is key in the recognition and elimination of invading pathogens, also in the removal of self-derived danger such as apoptotic cells, and it supports innate immune responses and the initiation of the general inflammatory reactions. The long prevailing classic view of complement was that of a serum-operative danger sensor and first line of defence system, however, recent experimental and clinical evidences have demonstrated that "local" tissue and surprisingly intracellular complement (the complosome) activation impacts on normal cell physiology. This review will focus on novel aspects of intracellular complement activation and its unexpected roles in basic cell processes such as metabolism. We also discuss what the existence of the complosome potentially means for how the host handles intracellular pathogens such as viruses.



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Intratumoral Fusobacterium nucleatum abundance correlates with macrophage infiltration and CDKN2A methylation in microsatellite-unstable colorectal carcinoma

Abstract

Fusobacterium nucleatum (Fn), a specific species of gut microbiota, has been suggested to be enriched in the microsatellite instability-high (MSI-H) molecular subtype of colorectal carcinomas (CRCs). However, the clinicopathologic and molecular factors that interact with Fn in MSI-H CRCs are poorly understood. In this study, 16S ribosomal RNA gene DNA sequence of Fn was quantitatively measured by real-time polymerase chain reaction in tumor DNA samples from a total of 160 surgically resected MSI-H CRC tissues. Each case was classified into one of the three categories based on the Fn DNA amount: Fn-high, Fn-low, and Fn-negative. The clinicopathologic and molecular associations of Fn in MSI-H CRCs were statistically analyzed. Among the 160 MSI-H CRC samples, 15 (9%), 92 (58%), and 53 (33%) cases were Fn-high, Fn-low, and Fn-negative, respectively. Compared with Fn-low/negative tumors, Fn-high MSI-H CRCs were significantly associated with a high density of CD68+ tumor-infiltrating macrophages (P = 0.019) and promoter CpG island hypermethylation of the CDKN2A (p16) gene (P = 0.008). There were also tendencies toward associations of Fn-high with the BRAF V600E mutation (P = 0.047) and active Crohn-like lymphoid reactions (P = 0.052) in MSI-H CRCs. However, Fn-high was not significantly associated with CD3+ T cell density, CD163+ M2 macrophage density or PD-L1 expression status. In conclusion, high amounts of intratumoral Fn are correlated with increased macrophage infiltration and CDKN2A promoter methylation in MSI-H CRCs.

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Gel-Forming Mucins and Aquaporin Gene Expression in Hearing Problems

This case-control study investigates the association of gel-forming mucins and aquaporin 5 gene expression with inflammation, effusion viscosity, and hearing loss in pediatric otitis media with effusion.

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Cognitive Training Program to Treat Tinnitus

To the Editor The recent randomized clinical trial by Kallogjeri et al on the effect of the Brain Fitness Program-Tinnitus (BFP-T) to treat tinnitus was interesting, but several limitations made me question the conclusions drawn by the authors.

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Cognitive Training Program to Treat Tinnitus—Reply

In Reply We thank Dr Stevelink for his interest in our work and his comments on our article describing the results of our open-label randomized clinical trial of Brain Fitness Training Program-Tinnitus (BFP-T) for adults with tinnitus. Unfortunately, we believe Dr Stevelink has incorrectly interpreted our study as a study that confirms the effect of BFP-T as a treatment for tinnitus. In our study, we did not observe nor did we conclude there were significant changes in THI and TFI scores associated with the BFP-T intervention. However, 10 of the 20 participants randomized to the BFP-T program self-reported improvement in their tinnitus perception, attention, memory, and concentration, as presented in detail in eTable 2 in Supplement 2. As can be seen in the eTable, the changes on the THI and TFI scores were inconsistent with each other and with subjective responses of perception of change. In our conclusions, we stated that participants endorsed improvements in these domains, suggesting that the computer-based cognitive brain training program is associated with self-reported changes in attention, memory, and perception of tinnitus. We also stated that several specific limitations prevented us from making a definitive conclusion regarding the role of this particular cognitive training program for the treatment of tinnitus.

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Modified Frailty Index Score and Perioperative Risk in Laryngectomy

This population-based study evaluates use of the Modified Frailty Index in estimation of outcomes in patients undergoing total laryngectomy

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Patient-Reported Outcome Measures in Upper Airway–Related Dyspnea

This systematic review of upper airway dyspnea–related patient-reported outcome measures evaluates each measure's developmental properties, validation, and applicability.

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The impact of the Court of Cassation on the Lower Judiciary and the de-facto precedent system in Belgium

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Editorial Board

Publication date: July 2017
Source:Clinical Immunology, Volume 180





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Leishmaniasis

Zusammenfassung

Das zeitlich verzögerte Auftreten einer Papel nach einem Auslandsaufenthalt kann auf das Vorliegen einer kutanen Leishmaniasis hinweisen. Histologisch zeigt sich eine granulomatöse Entzündungsreaktion, in den Histiozyten findet man in der Giemsa-Färbung intrazelluläre Parasiten. Mittels Polymerasekettenreaktion aus dem Gewebe oder der Kultur lassen sich potenzielle Differenzialdiagnosen ausschließen, aber auch die Leishmania-Subspezies identifizieren. Letzteres ist wichtig für die Wahl des optimalen Therapieregimes.

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Current challenges in hyperspectral X-ray transmission imaging

Throughout the last decades, photon-counting detectors have made spectral imaging possible. This allows for improved segmentation and identification of the different materials present in the sample under investigation. However, these detectors are often limited to a small number (1 to 8) energy bins [1], and due to the various interaction mechanisms in the imaging process the unambiguous identification of specific materials is not straight-forward [2]. Recently, a new type of detectors have been developed, which allow for 2D spectroscopic imaging, or hyperspectral imaging [3,4,5]. The output of these detectors is a complete X-ray spectrum for each individual pixel, hence creating a large number (typically in the order of 1000) monochromatic images. With this data, the interpretation and data analysis is more intuitive and requires less sample-specific calibration to allow for material identification, for both radiographic and tomographic datasets [6,7]. However, many challenges remain for this type of detectors. These are in the first place a consequence of the limited count-rate which can be achieved due to the complex readout mechanisms in these systems. In this presentation, we will elaborate on these limitations, and we will discuss potential solutions to these challenges.

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Articles 9(3) and 9(4) of the Aarhus Convention and Access to Justice before EU Courts in Environmental Cases: Balancing On or Over the Edge of Non-Compliance?

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Homelike thermoregulation: How physical coldness makes an advertised house a home

House brokers typically intuit that any type of warmth causes people to buy houses more frequently. Is this empirical reality? The authors investigated this through people's attachment towards advertised houses. A wealth of research has now linked thermoregulation to relationships (cf. IJzerman et al., 2015), and here the authors purport that this extends to people's relationships with house as a more novel solution to an ancient problem: shielding from the cold. The present package tests a preregistered idea that colder temperatures increase people's need to affiliate and, in turn, increase people's estimations of how homely a house is (measured through communality). The hypotheses of the first two studies were partly right: the authors only found that actual lower temperatures (not motivation and through a cup and outside temperature) induced people to find a house more communal, predicted by their need to affiliate. Importantly, this even predicts whether people find the house more attractive, and increases their willingness to pay for the house (Studies 1 and 2). The third study did not pan out as predicted, but still affected people's need to affiliate. The authors reason that this was caused by a methodological shortcoming (namely not as strongly being affected by temperature). The present work provides novel insights into how a house becomes a home. (C) 2015 Elsevier Inc. All rights reserved.

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MEN1 mutations and potentially MEN1 -targeting miRNAs are responsible for menin deficiency in sporadic and MEN1 syndrome-associated primary hyperparathyroidism

Abstract

Inherited, germline mutations of menin-coding MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), while somatic MEN1 mutations are the sole main driver mutations in sporadic primary hyperparathyroidism (PHPT), suggesting that menin deficiency has a central role in the pathogenesis of PHPT. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to investigate both the role of MEN1 mutations and potentially MEN1-targeting miRNAs as the underlying cause of menin deficiency in MEN1-associated and sporadic PHPT tissues. Fifty six PHPT tissues, including 16 MEN1-associated tissues, were evaluated. Diagnosis of MEN1 syndrome was based on identification of germline MEN1 mutations. In silico target prediction was used to identify miRNAs potentially targeting MEN1. Menin expression was determined by immunohistochemistry while expression of miRNAs was analyzed by quantitative real-time PCR. Sporadic PHPT tissues were subjected to somatic MEN1 mutation analysis as well. Lack of nuclear menin was identified in all MEN1-associated and in 28% of sporadic PHPT tissues. Somatic MEN1 mutations were found in 25% of sporadic PHPTs. The sensitivity and specificity of menin immunohistochemistry to detect a MEN1 mutation were 86 and 87%, respectively. Expression levels of hsa-miR-24 and hsa-miR-28 were higher in sporadic compared to MEN1-associated PHPT tissues; however, no difference in miRNA levels occurred between menin-positive and menin-negative PHPT tissues. Menin deficiency is the consequence of a MEN1 mutation in most menin-negative PHPT tissues. Elevated expression of hsa-miR-24 and hsa-miR-28 mark the first epigenetic changes observed between sporadic and MEN1-associated PHPT.

http://ift.tt/2s09Ffs

Multiple Desmoplastic Cellular Neurothekeomas in Child: Report of the First Oral Case and Review of the Literature

Abstract

Cellular neurothekeomas (CNs) are distinctive benign tumors of uncertain histogenesis, with predilection for the skin of the head and neck region. We describe the first case of multiple desmoplastic CNs (DCNs) affecting the oral cavity in a 9-year-old girl. Histopathologic evaluation showed a proliferation of spindle and epithelioid cells, forming nests and bundles, supported by exuberant fibrous stroma, as well as scattered multinucleated floret-like giant cells. The tumor cells were immunopositive for vimentin, CD63, CD56, whereas AE1/AE3, S100, CD34, α-SMA, GFAP, EMA, CD57 and NSE were negative. Ki-67 was <2%. Multiple DCNs should be considered in the differential diagnosis of oral nodular lesions.

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Malignant hypertension as a rare cause of thrombotic microangiopathy

Malignant hypertension can occasionally be associated with microangiopathic haemolytic anaemia. A 38-year-old male presented with nausea, vomiting, loss of appetite and oliguria for 2 weeks. He was diagnosed with hypertensive emergency with cardiac and renal dysfunction. Interestingly, further workup was diagnostic for the presence of thrombotic microangiopathy (TMA): haemoglobin =12.7 g/dL, indirect bilirubin =2.0 mg/dL, haptoglobin ≤6 mg/dL, platelet count =121 000/μL and schistocytes on peripheral smear. At the outset, the cause of TMA was unclear. Patient denied having diarrhoea, making haemolytic uremic syndrome less likely. A normal ADAMTS13 activity test ruled out thrombotic thrombocytopaenic purpura. Malignant hypertension induced TMA was highest on the differential and plasma exchange was deferred. Renal biopsy revealed features of TMA and malignant nephrosclerosis. Patient eventually became dialysis dependent. Aggressive blood pressure control was obtained with multiple medications.

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Intrahepatic fetus: unusual image of an intratumoural haemorrhage

Description

A 65-year-old man presented to our institution with acute onset, right upper quadrant pain, on a background of rheumatoid arthritis and asthma. He was a lifelong non-smoker, with minimal alcohol consumption and no intravenous drug use. CT and MRI demonstrated a large tumour involving the entire segment IV of the liver positioned between the middle and the left hepatic veins. A T1-weighted axial MRI at the level of right hepatic vein demonstrated an odd, fetus-like lesion within the mass (figure 1). Junior medical staff questioned whether this could be a primary hepatic pregnancy. However, they were reassured that this image portrayed an intraparenchymal bleed, consistent with hepatocellular carcinoma (HCC). A diagnosis of HCC was confirmed by non-invasive criteria for diagnosing HCC recommended by both the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver consensus statement.

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Mediastinal seminoma presenting with superior vena cava syndrome

We present a rare cause of superior vena cava syndrome (SVC) in a previously healthy male aged 31 years. Malignancy was suspected due to unintentional weight loss and childhood exposure to radioactive fallout from a nuclear facility accident. A very large anterior mediastinal mass was identified and demonstrated to be an extragonadal seminoma. Extragonadal germ cell tumours are rare tumours with a high potential for cardiovascular, pulmonary and vascular sequelae. Studies have documented an increased risk of developing seminoma in patients with radioactive exposure. Chemotherapy was initiated, during which the patient experienced progressive and new symptoms, found to be due to extensive thromboembolic disease, which responded well to anticoagulation. Seventy-two months after completing chemotherapy, without need for surgical management, he remains free of the disease.

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Pituitary abscess

Pituitary abscess is an uncommon pituitary lesion. Its clinical diagnosis can be difficult to distinguish from other pituitary lesions. This pathology is characterised by vague symptoms of headaches, generalised tiredness and hypopituitarism manifestations. A history of recent meningitis, paranasal sinusitis or head surgery can be a suggestive of the source of infection.

A 20-year-old man was admitted to neurosurgery department with complain of headache, fatigue, polyuria, polydipsia, blurred vision and sexual dysfunction. MRI of the head revealed a suprasellar mass that was centrally hyperintense lesion on T2-weighted images with peripheral hypointensity and isointense centrally on T1 images with peripheral hyperintensity images. Treatment of this lesion pituitary abscess was surgical drainage of the pituitary area through a trans-sphenoidal approach and broad spectrum antibiotic therapy with ceftriaxone, metronidazole and vancomycin for 6 weeks. The patient continues to have pituitary insufficiency and treated with oral hydrocortisone.

Although pituitary abscess is a rare condition, it should always be kept in mind when evaluating a patient with hypopituitarism. After the diagnosis, the surgery and antibiotics should be commenced rapidly. The outcome is usually good with proper treatment.

http://ift.tt/2r6cDjA

A case of a chronic salmonella infection following Roux-en-Y gastric bypass surgery, treated successfully by a laparoscopic cholecystectomy

We report a case of chronic infection caused by Salmonella and cured by a laparoscopic cholecystectomy after Roux-en-Y gastric bypass (RYGB) surgery for obesity. This patient presented with a 2-year history of chronic abdominal pain, loose stools and excessive weight loss. Her stool and urine cultures were positive for Salmonella. Despite multiple courses of antibiotics, she remained positive.

After undergoing a laparoscopic cholecystectomy, the patient became asymptomatic and stools remained negative. In chronic carriers for Salmonella, the gall bladder is the common reservoir for the bacteria and removing it is usually curative.

The possibility that the source of the may be in the biliary limb of her bariatric procedure and not in the gall bladder remained a concern.

In patients who have had a RYGB, cholecystectomy is an effective treatment.

All patients presenting with abdominal symptoms following RYGB should have stool and urine cultures taken as part of their work up.

http://ift.tt/2rQ6eGa

Surgical management of isolated mesenteric autoimmune disease: addressing the spectrum of IgG4-related disease and sclerosing mesenteritis

IgG₄-related disease (IgG₄-RD) is a rare form of autoimmune sclerosing disease, characterised by elevated serum IgG₄ and tissue IgG₄ levels, specific histopathological findings, multiorgan involvement and adequate response to glucocorticoid treatment. The low incidence and the heterogeneous nature of the disease has made consensus on diagnostic criteria for IgG₄-RD difficult. Whether sclerosing mesenteritis (SM) is considered a manifestation of IgG₄-RD is strongly debated. We present the case of a patient with a history of rheumatoid arthritis who presented with a calcified abdominal mass. She was found to have an isolated, pedunculated mesenteric mass positive for IgG₄ and concurrently elevated serum IgG₄ levels. Clinical features did not classify her disease as either SM or IgG₄-RD as currently described in consensus statements. Concurrent diagnoses of IgG₄-RD, SM and other autoimmune disorders, as well as postoperative recommendations for resected isolated IgG₄-positive masses, are discussed.

http://ift.tt/2rPXMqm

Isolated gastric sarcoidosis: a rare entity

We present a case of isolated granulomatous gastritis in a 21-year-old woman. Initial symptoms included nausea, vomiting and inability to tolerate oral intake. An upper oesophagogastroduodenoscopy revealed nodular and thickened mucosa with histological findings of granulomatous gastritis. Infectious, inflammatory and malignant causes were excluded prior to making a diagnosis of gastric sarcoidosis.

http://ift.tt/2r6cCw2

Congenital prepubic sinus (an epispadiac variant of dorsal urethral duplication) with dorsal penile curvature in an adult man: a rare association

Urethral duplication is among a very rare congenital disorder with multiple anatomical variants reported. Urethral duplication of complete type is usually diagnosed during childhood with urinary incontinence or double urinary stream as common presentation. However, patients with incomplete urethral duplication usually present with intermittent mucous discharge from the accessory urethral opening. A 20-year-old man presented to us with intermittent mucous discharge from the accessory opening along with dorsal penile curvature making sexual intercourse very difficult. The epispadiac urethral tract with proximal fibrous tract was excised, and the dorsal penile curvature was corrected by ventral plication, implicating that the fibrous cord may be the causative factor for the development of dorsal curvature.

http://ift.tt/2rPRsiP

Persistent lesion hyperintensity on brain diffusion-weighted MRI is an early sign of intravascular lymphoma

A 63-year-old man presented with right-sided hemianopia and unsteady gait. Brain MRI revealed multiple hyperintense infarct-like lesions on diffusion-weighted images (DWI). Hyperintensity persisted in some of these lesions even after 6 weeks, although his symptoms were ameliorated then. The patient developed episodic dizziness and a transient event of apraxia at 18 weeks after the first episode. Brain MRI revealed additional hyperintense lesions on DWI, which persisted even after 7 weeks. Eventually, the patient manifested cauda equina syndrome 39 weeks after the first episode. Brain MRI showed the presence of new lesions in addition to the persistent hyperintense lesions on DWI over 21 weeks in the right frontal lobe. Based on laboratory findings and the pathological assessment of bone marrow and random skin biopsies, the patient was diagnosed with intravascular lymphoma (IVL). Persistent hyperintense lesions on DWI of brain MRI may precede the clinical exacerbation of IVL.

http://ift.tt/2r5PCgx

Delayed progression of bulls eye maculopathy

Chloroquine-induced maculopathy may progress years after drug cessation and an apparent period of visual stability. Both doctor and patients should be fully aware of the risks of retinal toxicity, including delayed onset and progression. It is therefore crucial that regular monitoring continues in affected patients, long after the initial diagnosis of maculopathy.

http://ift.tt/2rQ6Iwa

Primary myeloid sarcoma of small bowel

Description

A 45-year-old woman presented with severe lower abdominal pain and vomiting. On physical examination, she was found to have tenderness in the suprapubic region and right iliac fossa. An ultrasound abdomen performed to rule out acute appendicitis and pelvic inflammatory disease was not contributory. Blood parameters were within normal limits. As the patient continued to be symptomatic, a contrast-enhanced CT of the abdomen was performed. It revealed eccentric focal bowel wall thickening involving the ileum measuring 3.3x2.4 cm, with homogeneous enhancement on postcontrast images causing mild luminal compromise (figures 1, figure 2). Oral contrast was noted to pass distally with no proximal hold-up. Mild dilatation of proximal ileal loops with diffuse wall thickening was noted (figure 3). No perifocal mesenteric fat infiltration was identified. Few discrete enlarged perifocal lymph nodes were noted (figure 4). There was no retroperitoneal lymphadenopathy. In view of...

http://ift.tt/2r5T6zL

Port site recurrence after laparoscopic radical nephrectomy: a case report

Due to the recent development of laparoscopic devices, laparoscopic radical nephrectomy is the standard procedure for localized renal cell carcinoma. However, some studies have reported postoperative port site...

http://ift.tt/2sH1oeq

Welke problemen zouden we kunnen oplossen met al die ontweken belastingen?

Fiscal experts and government ministers stated recently that the rich are too highly taxed. I try to give answers from an ethical humanist viewpoint. For me (and probably for most people ) the taxes paid are less important than how much remains for spending. The taxes paid by individuals are not public in Belgium; the average conceals the extreme variation. We know from the numerous "leaks" that there are massive tax avoidance and evasion by corporations and by the wealthy. But we should consider what we all expect from society: schools, social housing, healthcare, transport, climate change…To-day even security services and justice lack the necessary manpower. The wars in which Belgium participates must be paid. Homeless and refugees need our urgent help. The private sector does not fill these needs because this is not profitable. So public authorities must provide financing from tax returns. As a consequence, tax returns should not be lowered, but improved.

http://ift.tt/2s7N4yO

Multiple Desmoplastic Cellular Neurothekeomas in Child: Report of the First Oral Case and Review of the Literature

Abstract

Cellular neurothekeomas (CNs) are distinctive benign tumors of uncertain histogenesis, with predilection for the skin of the head and neck region. We describe the first case of multiple desmoplastic CNs (DCNs) affecting the oral cavity in a 9-year-old girl. Histopathologic evaluation showed a proliferation of spindle and epithelioid cells, forming nests and bundles, supported by exuberant fibrous stroma, as well as scattered multinucleated floret-like giant cells. The tumor cells were immunopositive for vimentin, CD63, CD56, whereas AE1/AE3, S100, CD34, α-SMA, GFAP, EMA, CD57 and NSE were negative. Ki-67 was <2%. Multiple DCNs should be considered in the differential diagnosis of oral nodular lesions.

http://ift.tt/2rEN7AD

Effect of cochlear implant surgery on vestibular function: meta-analysis study

Abstract

Importance

Vestibular disorders have been reported following cochlear implant (CI) surgery, but the literature shows a wide discrepancy in the reported clinical impact. The aim of this meta-analysis is to quantify the effect of CI before and after surgery on the outcomes of vestibular tests, postural stability, and subjective perception of dizziness.

Objective

To evaluate the effects of CI surgery on vestibular function in adult patients (≥18 years) with sensorineural hearing loss who underwent unilateral or bilateral implantation.

Data sources

MEDLINE, PubMed, Web of Science and Cochrane Library from January 1, 1995, through July 12, 2016.

Study selection

Published studies of adult patients who received unilateral or bilateral CIs and whose vestibular function or postural stability was assessed before and after surgery.

Data extraction

From each study, test results before and after surgery were compared, for the following five tests: clinical head impulse test (HIT); bi-thermal caloric irrigation of the horizontal semicircular canal; vestibular evoked myogenic potential (VEMP); dizziness handicap inventory (DHI); and computerized dynamic posturography (CDP).

Results

Twenty-seven studies met all inclusion criteria. Most studies performed either bi-thermal caloric irrigation and/or VEMP, with fewer studies investigating changes in HIT, posturography or DHI. CI surgery significantly affected the results of caloric and VEMP testing. However, HIT results, posturography, and DHI, scores were not significantly affected after CI surgery.

Conclusions and relevance

CI surgery has a significant negative effect on the results of caloric as well as VEMP tests. No significant effect of CI surgery was detected in HIT, posturography, or DHI scores. Overall, the clinical effect of CI surgery on the vestibular function was found to be insignificant. Nonetheless, the potential effects of surgery on the vestibular system should be discussed with CI candidates before surgery.

http://ift.tt/2sHj2Pg

De Programmatische Aanpak Stikstof (PAS): Van een verstands- naar gelukkig huwelijk tussen economie en natuur?

http://ift.tt/2rZFzJn

De EU Habitatrichtlijn en atmosferische stikstofdepositie: dura lex, sed lex

http://ift.tt/2rZYsM0

A Communist Compromise: Introducing Willem Elsschot’s Cheese Soviet Style

This contribution discusses the 1972 Soviet preface to one of Flanders' favourite novels, Willem Elsschot's Kaas (Cheese). With the help of its fairly recent reception in the Anglophone world, as a means of comparison, I scrutinized how the Russian editors tried to deal with the 'un-Soviet' topics of commerce and capitalism which the novel has so famously thematized.

http://ift.tt/2sXtUHV

Saving the Common Hamster from extinction through the EU Habitats Directive: A mandatory recovery effort, a remediation of past non-compliance or an exercise in futility?

http://ift.tt/2rZYlQA

Vlaams omgevingsrecht: (g)een toren van Babel?

http://ift.tt/2sXTigN

Na Noorse klimaatzaak is het hoog tijd voor een Vlaamse klimaattoets?

http://ift.tt/2rZUJ1h

The Best Interests of the Child in Divorce Proceedings: Achieving Child-friendly Litigation in the Quest for Fair Custody and Visiting Rights

http://ift.tt/2sXIjE2

Proactive habitat restoration and the avoidance of adverse effects on protected areas: Development project review in Europea after Orleans?

http://ift.tt/2r5LRb6

Commentaar bij art. 23 Pandwet

http://ift.tt/2rPROpN

Multiple Desmoplastic Cellular Neurothekeomas in Child: Report of the First Oral Case and Review of the Literature

Abstract

Cellular neurothekeomas (CNs) are distinctive benign tumors of uncertain histogenesis, with predilection for the skin of the head and neck region. We describe the first case of multiple desmoplastic CNs (DCNs) affecting the oral cavity in a 9-year-old girl. Histopathologic evaluation showed a proliferation of spindle and epithelioid cells, forming nests and bundles, supported by exuberant fibrous stroma, as well as scattered multinucleated floret-like giant cells. The tumor cells were immunopositive for vimentin, CD63, CD56, whereas AE1/AE3, S100, CD34, α-SMA, GFAP, EMA, CD57 and NSE were negative. Ki-67 was <2%. Multiple DCNs should be considered in the differential diagnosis of oral nodular lesions.

http://ift.tt/2rEN7AD

Shakespearean maternities: Crises of conception in early modern England

Laoutaris, C; (2005) Shakespearean maternities: Crises of conception in early modern England. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2r9I3At

The impact of tooth brushing on enamel affected by Molar Incisor Hypomineralisation (MIH)

Alqahtani, MR; (2017) The impact of tooth brushing on enamel affected by Molar Incisor Hypomineralisation (MIH). Doctoral thesis, UCL (University College London).

http://ift.tt/2rF155e

A Qualitative Analysis of Life Skills needed for Independence in Adulthood – Perspectives from Young People with Moderate Learning Difficulties, their Parents and their Teachers

Shah, S; (2017) A Qualitative Analysis of Life Skills needed for Independence in Adulthood – Perspectives from Young People with Moderate Learning Difficulties, their Parents and their Teachers. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2r9igZs

Role, Relationship and Friend for Life: How Independent Visitors promote the Learning and Wellbeing of Looked After Children

Clancy, D; (2017) Role, Relationship and Friend for Life: How Independent Visitors promote the Learning and Wellbeing of Looked After Children. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2rF3w8f

A mixed methods pilot study evaluating the effectiveness of a mindfulness-based intervention for exam-related anxiety in secondary school settings

Casson, SA; (2017) A mixed methods pilot study evaluating the effectiveness of a mindfulness-based intervention for exam-related anxiety in secondary school settings. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2r9yWQz

Assessing the applied anatomy knowledge of medical students: the effect of visual resources on preparing them to become new doctors

Sagoo, MG; (2017) Assessing the applied anatomy knowledge of medical students: the effect of visual resources on preparing them to become new doctors. Doctoral thesis, UCL (University College London).

http://ift.tt/2rF5NAk

The Contribution of General Practice Placements to Medical Education: An Analysis of the Construction of General Practice Placement Knowledge in Published Medical Education Research

Park, SE; (2017) The Contribution of General Practice Placements to Medical Education: An Analysis of the Construction of General Practice Placement Knowledge in Published Medical Education Research. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2r9zu8R

A description of some of the features of general practice consultations in a clinic in India with reference to the Clinical Skills Assessment (CSA) of the United Kingdom Royal College of General Practitioners

Mohanna, K; (2017) A description of some of the features of general practice consultations in a clinic in India with reference to the Clinical Skills Assessment (CSA) of the United Kingdom Royal College of General Practitioners. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2rF5KEF

Outcomes and current perspectives in total ankle replacement surgery

Zaidi, SMR; (2017) Outcomes and current perspectives in total ankle replacement surgery. Doctoral thesis, UCL (University College London).

http://ift.tt/2r9Iqer

Atezolizumab Combinations With Chemotherapy for Anaplastic and Poorly Differentiated Thyroid Carcinomas

Conditions:   Malignant Neoplasms of Thyroid and Other Endocrine Glands;   Anaplastic Thyroid Carcinoma;   Poorly Differentiated Thyroid Cancer
Interventions:   Drug: Nab-paclitaxel - INDUCTION COHORT;   Drug: Paclitaxel - INDUCTION COHORT;   Drug: Vemurafenib - COHORT 1;   Drug: Cobimetinib - COHORT 1;   Drug: Atezolizumab - COHORT 1;   Drug: Bevacizumab - COHORT 3;   Drug: Nab-paclitaxel - COHORT 4;   Drug: Paclitaxel - COHORT 4;   Drug: Cobimetinib - COHORT 2;   Drug: Atezolizumab - COHORT 2;   Drug: Atezolizumab - COHORT 3;   Drug: Atezolizumab - COHORT 4
Sponsors:   M.D. Anderson Cancer Center;   Genentech, Inc.
Not yet recruiting - verified June 2017

http://ift.tt/2rZvJXL

Maintenance Therapy of Apatinib After Chemoradiotherapy in Nasopharyngeal Carcinoma With Metastasis

Condition:   Nasopharyngeal Neoplasms
Intervention:   Drug: Apatinib
Sponsors:   Sichuan Cancer Hospital and Research Institute;   Jiangsu HengRui Medicine Co., Ltd.
Recruiting - verified June 2017

http://ift.tt/2sXdP51

The Study of Early Stage Osteonecrosis of Femoral Head With Human Umbilical Cord Mesenchymal Stem Cells

Condition:   Osteonecrosis of Femoral Head
Interventions:   Drug: Allogeneic umbilical cord mesenchymal stem cells (SCLnow 19#);   Procedure: core decompression
Sponsor:   Sclnow Biotechnology Co., Ltd.
Not yet recruiting - verified May 2017

http://ift.tt/2rZtB2j

Correlation of FAZA PET Hypoxia Imaging To 3D Histology in Oral Tongue Cancer

Condition:   Tongue Cancer
Interventions:   Radiation: (18)F-Fluoroazomycin arabinoside;   Drug: Pimonidazole
Sponsors:   Sunnybrook Health Sciences Centre;   Sunnybrook Research Institute;   University of Toronto
Not yet recruiting - verified June 2017

http://ift.tt/2rZtALN

Spectrum of genetic mutations in de novo PUNLMP of the urinary bladder

Abstract

Our group and others have previously demonstrated the presence of TERT promoter mutations (TERT-mut) in 60–80% of urothelial carcinomas and some of their histologic variants. Five other genes have been frequently implicated in bladder cancer: FGRF3, TP53, PIK3CA, HRAS, and CDKN2A. In the current study, we sought to determine the prevalence of mutations in TERT and these five other genes in de novo papillary urothelial neoplasms of low malignant potential (PUNLMP) of the urinary bladder. A retrospective search of our archives for PUNLMP was performed and 30 de novo cases were identified and included in the study. We found mutations in TERT (TERT-mut) and FGFR3 (FGFR3-mut) to be the most common alterations in the cohort (63 and 60%, respectively). The majority of the TERT-mut-positive tumors (84%) had a g.1295228C > T alteration with the remaining tumors demonstrating g.1295250C > T. Approximately one fourth of tumors had TP53 mutations. These findings support the potential utility of a uniform genetic mutation panel to detect bladder cancers of various subtypes.

http://ift.tt/2sXOLea

Adaptation to fragmentation : evolutionary dynamics driven by human influences

Fragmentation-the process by which habitats are transformed into smaller patches isolated from each other-has been identified as a major threat for biodiversity. Fragmentation has well-established demographic and population genetic consequences, eroding genetic diversity and hindering gene flow among patches. However, fragmentation should also select on life history, both predictably through increased isolation, demographic stochasticity and edge effects, and more idiosyncratically via altered biotic interactions. While species have adapted to natural fragmentation, adaptation to anthropogenic fragmentation has received little attention. In this review, we address how and whether organisms might adapt to anthropogenic fragmentation. Drawing on selected case studies and evolutionary ecology models, we show that anthropogenic fragmentation can generate selection on traits at both the patch and landscape scale, and affect the adaptive potential of populations. We suggest that dispersal traits are likely to experience especially strong selection, as dispersal both enables migration among patches and increases the risk of landing in the inhospitable matrix surrounding them. We highlight that suites of associated traits are likely to evolve together. Importantly, we show that adaptation will not necessarily rescue populations from the negative effects of fragmentation, and may even exacerbate them, endangering the entire metapopulation. This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'.

http://ift.tt/2sHdhBa

Gedenken wij de Brusselse bedelaars

http://ift.tt/2s7NnJS

Inleiding

http://ift.tt/2sGT4eG

Milieueffectrapportage: een kennismaking

http://ift.tt/2s7uff8

Handboek Milieueffectrapportagerecht

http://ift.tt/2sH0CxW

Migrating common toads (Bufo bufo) in rural temperate regions: reservoirs of Salmonella?

Salmonella infections in amphibians are supposedly highly prevalent. Migrating common amphibian species in cultivated areas such as common toads (Bufo bufo) may thus promote spread and zoonotic transfer of Salmonella to humans, both indirectly by crop and livestock contamination and by direct contact. Between February and April 2011, the intestinal content of 1,740 samples of road-killed migrating common toads in five Flemish provinces of Belgium was examined for the presence of Salmonella using bacterial culture and PCR. All the samples were negative. These results suggest that the role of migrating common toads in maintaining the infection cycle of Salmonella in northern European temperate regions is negligible.

http://ift.tt/2s7T8Hj

Generation of a nanobody targeting the paraflagellar rod protein of trypanosomes

Trypanosomes are protozoan parasites that cause diseases in humans and livestock for which no vaccines are available. Disease eradication requires sensitive diagnostic tools and efficient treatment strategies. Immunodiagnostics based on antigen detection are preferable to antibody detection because the latter cannot differentiate between active infection and cure. Classical monoclonal antibodies are inaccessible to cryptic epitopes (based on their size-150 kDa), costly to produce and require cold chain maintenance, a condition that is difficult to achieve in trypanosomiasis endemic regions, which are mostly rural. Nanobodies are recombinant, heat-stable, small-sized (15 kDa), antigen-specific, single-domain, variable fragments derived from heavy chain-only antibodies in camelids. Because of numerous advantages over classical antibodies, we investigated the use of nanobodies for the targeting of trypanosome-specific antigens and diagnostic potential. An alpaca was immunized using lysates of Trypanosoma evansi. Using phage display and bio-panning techniques, a cross-reactive nanobody (Nb392) targeting all trypanosome species and isolates tested was selected. Imunoblotting, immunofluorescence microscopy, immunoprecipitation and mass spectrometry assays were combined to identify the target recognized. Nb392 targets paraflagellar rod protein (PFR1) of T. evansi, T. brucei, T. congolense and T. vivax. Two different RNAi mutants with defective PFR assembly (PFR2(RNAi) and KIF9B(RNAi)) were used to confirm its specificity. In conclusion, using a complex protein mixture for alpaca immunization, we generated a highly specific nanobody (Nb392) that targets a conserved trypanosome protein, i.e., PFR1 in the flagella of trypanosomes. Nb392 is an excellent marker for the PFR and can be useful in the diagnosis of trypanosomiasis. In addition, as demonstrated, Nb392 can be a useful research or PFR protein isolation tool.

http://ift.tt/2sGT3aC

Can routinely recorded reproductive events be used as indicators of disease emergence in dairy cattle?: an evaluation of 5 indicators during the emergence of bluetongue virus in France in 2007 and 2008

In response to increasing risks of emerging infectious diseases, syndromic surveillance can be a suitable approach to detect outbreaks of such diseases across a large territory in an early phase. To implement a syndromic surveillance system, the primary challenge is to find appropriate health-related data. The objective of this study was to evaluate whether routinely collected dates of reproductive events in dairy cattle could be used to build indicators of health anomalies for syndromic surveillance. The evaluation was performed on data collected in France between 2003 and 2009. First, a set of 5 indicators was proposed to assess several types of reproductive disorders. For each indicator, the demographic coverage over the total number of cattle at risk was analyzed in time and space. Second, the ability to detect an emerging disease in an early phase was retrospectively evaluated during epidemics of bluetongue serotypes 1 and 8 (BTV-1, BTV-8) in France in 2007 and 2008. Reproductive indicators were analyzed weekly during these epidemics for each indicator in each infected French district (16 in 2007 and 50 in 2008 out of 94 districts). The indicators were able to detect the BTV epidemics despite their low demographic coverage on a weekly basis relatively to total number of cattle (median = 1.21%; range = 0-11.7%). Four indicators related to abortions, late embryonic death, and short gestations were abnormally elevated during both BTV epidemics. Median times to abnormal elevations in these indicators were 20 to 71 d after the first notification of clinical signs of BTV by veterinarians. These results demonstrate that reproduction data can be used as indicators of disease emergences, whereas in the specific case of these BTV epidemics, detection via these indicators was later than clinical detection by veterinarians. The emergence of bluetongue in 2007 in France was associated with gestations that were a few days shorter than expected. A short gestation indicator underwent high elevations relative to prior random fluctuations and was the earliest (out of the 4 indicators) to show abnormal elevations, making it possible to detect this emergence.

http://ift.tt/2s7B14d

No evidence of coronavirus infection by reverse transcriptase-PCR in bats in Belgium

No coronavirus was detected by PCR in lung and intestine samples of 100 bats, mostly common pipistrelles (Pipistrellus pipistrellus), collected dead between 2008 and 2013 for rabies surveillance in Belgium. The negative results contrast with the high prevalence of coronaviruses detected in fecal pellets from live-captured bats in some European countries.

http://ift.tt/2sH0D4Y

Road-killed common toads (Bufo bufo) in Flanders (Belgium) reveal low prevalence of ranaviruses and Batrachochytrium dendrobatidis

Road-killed common toads (Bufo bufo; n=1,740) from Flanders, Belgium, were tested for ranavirus and Batrachochytrium. dendrobatidis. (Bd) using polymerase chain reaction. Both infections were present at a very low prevalence (<0.2% with a confidence interval of 95% for ranavinis and 0.63% for Bd).

http://ift.tt/2s7Aq2r

Serologic cross-reactivity with pandemic (H1N1) 2009 virus in pigs, Europe

We tested serum samples from pigs infected or vaccinated with European swine influenza viruses (SIVs) in hemagglutination-inhibition assays against pandemic (H1N1) 2009 virus and related North American SIVs. We found more serologic cross-reaction than expected. Data suggest pigs in Europe may have partial immunity to pandemic (H1N1) 2009 virus.

http://ift.tt/2sGTYbj

Pneumococcal serotypes in children in 4 European countries

After heptavalent pneumococcal conjugate vaccine (PCV7) was marketed in France, Spain, Belgium, and England and Wales (United Kingdom), invasive disease from non-PCV7 serotypes (NVT) increased. Adjusted serotype-specific incidences among children <15 years of age were compared between 1999-2002 (prevaccine) and 2005-2006 (postmarketing). Vaccine coverage increased to approximate to 32%-48% in France, Spain, and Belgium but remained <1% in England and Wales. Serotype 1 incidence rose in all age groups and countries (incidence rate ratio [IRR] 1.3-4.2; p<0.004), independently of PCV7 use, but incidence of serotypes 7F and 19A increased most in France, Spain, and Belgium (IRR 1.9-16.9 in children <5 years; p<0.001), where PCV7 coverage was greater. Vaccine-induced replacement of PCV7 serotypes possibly contributed to NVT increases, as did secular trends. New vaccines targeting these serotypes are available, but serotype dynamics needs further exploration that accounts for underreporting and prevaccine trends.

http://ift.tt/2s7ARdp

Definition of the interacting interfaces of Apobec3G and HIV-1 Vif using MAPPIT mutagenesis analysis

http://ift.tt/2sGMbtT

New and re-emerging infectious diseases: epidemics in waiting

http://ift.tt/2s7MxNi

Transformation of the Cassation Mechanism: France, the Netherlands and Begium on the Road to Terra Incognita?

http://ift.tt/2rEMJlE

Redden Amerikaanse rechters het klimaat?

http://ift.tt/2r9h5ZS

In naam van de Zenne, beschuldigde sta op!

http://ift.tt/2rEH2UK

The Next Generation vs Trump

http://ift.tt/2r98xlG

Atmospheric pressure plasma activation of PP films with a localized μplasma

Polypropylene (PP) films are locally plasma treatedwith a single line pattern using a μplasma needle set-up with micro scale accuracy and resolution. The two main plasma treatment conditions, number of treatment repeats and applied power, have been varied and their influence on the surface characteristics has been investigated. X-ray photoelectron spectroscopy (XPS) mapping measurements have been carried out to show the distribution of oxygen functional groups across sections of the plasma treated line patterns. These measurements have been correlated with water contact angle (WCA) results and showed that the created polar oxygenated functionalities are responsible for a sharp local increase in wettability. Increasing power and treatment repeats resulted in an improvement inwetting behavior of PP films and led towider tracks with higher percentages of incorporated oxygen across the treatment patterns. AFM analysis of a treated straight line also showed that the center of the track line has a higher roughness than the border parts. Increasing power and number of treatment repeats results in a progressive increase of surface roughness and the generation of a granular topography. It has been shown that increasing the power has a more pronounced effect on the PP morphology than the variation of treatment time.

http://ift.tt/2rECIom

Cellular and molecular pathways of structural damage in rheumatoid arthritis

Abstract

Structural damage of cartilage and bone tissue is a hallmark of rheumatoid arthritis (RA). The resulting joint destruction constitutes one of the major disease consequences for patients and creates a significant burden for the society. The main cells executing bone and cartilage degradation are osteoclasts and fibroblast-like synoviocytes, respectively. The function of both cell types is heavily influenced by the immune system. In the last decades, research has identified several mediators of structural damage, ranging from infiltrating immune cells and inflammatory cytokines to autoantibodies. These factors result in an inflammatory milieu in the affected joints which leads to an increased development and function of osteoclasts and the transformation of fibroblast-like synoviocytes towards a highly migratory and destructive phenotype. In addition, repair mechanisms mediated by osteoblasts and chondrocytes are strongly impaired by the presence of pro-inflammatory cytokines. This article will review the current knowledge on the mechanisms of joint inflammation and the destruction of bone and cartilage.

http://ift.tt/2rZhylE

Justice pour les personnes déplacées en RDC: introduction

http://ift.tt/2rZfsBZ

Accès à la justice en RDC

http://ift.tt/2sXzsCe

Quête de justice: conflit, déplacement et justice dans le Haut-Uélé, RDC

http://ift.tt/2rZ9xx4

Habitat Restoration Measures as Facilitators for Economic Development within the Context of the EU Habitats Directive: Balancing No Net Loss with the Preventive Approach?

http://ift.tt/2sXixzT

Health risk/benefit information for consumers of fish and shellfish: FishChoice, a new online tool

It is well known that due to the content in omega-3 fatty acids, consumption of fish and shellfish is beneficial for human cardiovascular health. However, a number of recent studies have shown that fish consumption may be also a potential dietary source of exposure to various environmental pollutants with well-known potential adverse effects on human health. Moreover, there is still a lack of information regarding levels of emerging contaminants in fish and shellfish, in particular among consumers and stakeholders. Within the ECsafeSEAFOOD FP7 project, a wide variety of emerging contaminants including brominated flame retardants, pharmaceuticals, perfluoroalkyl substances, musk fragrances, polycyclic aromatic hydrocarbons, UV-filters and endocrine disruptors, as well as inorganic arsenic and methyl mercury, were analyzed in fish and shellfish samples collected all over the European Union. These data, together with those regarding nutrient concentrations from different European food composition databases, were integrated into a new online tool, called FishChoice. In this paper, we report how Fish Choice was designed and present its main improvements compared to previous tools or software programs, in terms of selected pollutants, number of species, and specific recommendations for an optimal consumption of fish and shellfish. (C) 2017 Elsevier Ltd. All rights reserved.

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Nitrogen deposition, habitat restoration and the EU Habitats Directive: moving beyond the deadlock with the dutch programmatic nitrogen approach?

http://ift.tt/2rZo77v

Making sense of a messy object : how to use social topology as an analytic tool for ethnography of objects

This theoretical-methodological essay seeks to answer the question, "How can one make sense of a messy object?" The denomination "messy" refers to a situation in which the object of ethnographic research is interpretatively complex to such a degree that the ethnographer may become trapped in the attempt to capture all of the various facets of the object at once (Law & Singleton, 2005). We focus on blood as a messy object and study it in the context of a Belgian Blood Establishment, the organization charged with the provision of safe and sufficient amounts of blood for a region. Existing research has dealt with the messiness of blood through epistemological response, casting it in four "blood stories" – the gift relationship, the blood economy, biological citizenship, and blood safety. While these stories have enhanced our understanding of blood, we argue that they are examples of perspectivalism (Mol, 2002). Although they do frame blood from various angles, they fail to grasp the entanglement of technological, biomedical, political, and socio-technical aspects of this "bio-object" (Vermeulen et al., 2012). This essay takes a different turn and attempts to mediate the difficulties by formulating an ontological response through careful consideration of the social topology framework (Law & Mol, 2001; Mol & Law, 1994). For every space (Euclidian, network, fluid, and fire), we provide a comprehensive summary of the theory, after which we delineate specific elements from this theory to induce conceptual sensitivity and propose research questions that follow from these elements. In this endeavor, we attempt to highlight the unique value of this framework for the ethnography of objects, as compared to the frameworks that initially gave rise to the theory.

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Non-Regression Clauses in Times of Ecological Restoration Law: Article 6(2) of the EU Habitats Directive as an unusual ally to restore Natura 2000?

http://ift.tt/2rZiKW6

Besoins, stratégies et mécanismes en matière de justice pour les personnes déplacées

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DNA adduct profiling of in vitro meat digests as a means to assess red vs. white meat genotoxicity

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High susceptibility prevalence for F4⁺ and F18⁺ Escherichia coli in Flemish pigs

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The role of teacher trust in segregated elementary schools: a multilevel repeated measures examination

This study aims to investigate how teachers' trust in their students relates to reading comprehension achievement in socially and ethnically segregated elementary schools in Flanders (Belgium) by taking into account class composition characteristics. It is examined how student variables, ethnic diversity and the proportion of non-native students in the class, and teachers' trust in their students relate to reading comprehension achievement and learning growth. A 3-level multivariate repeated measures analysis was conducted. At 2 measurement occasions, reading tests and questionnaires were administered to a sample (n = 417) of 7- and 8-year-old students in 32 classes. Teachers' trust in their students was found to be a key factor relating to learning growth in reading comprehension, and mediated the relationship between the level of ethnic diversity in the class and learning growth. Teachers with a higher level of trust in their students seem to foster more learning growth in reading comprehension.

http://ift.tt/2rZ7Bod