Head and Neck Diseases by Alexandros G.Sfakianakis: 10/05/18

Παρασκευή 5 Οκτωβρίου 2018

Correction to: Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction

Upon publication of the original article [1], the authors reported the following funding information was omitted: Publication supported by Wroclaw Centre of Biotechnology, programme The Leading National Resear...

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Diadenosine-Polyphosphate Analogue AppCH2ppA Suppresses Seizures by Enhancing Adenosine Signaling in the Cortex

Abstract

Epilepsy is a multifactorial disorder associated with neuronal hyperexcitability that affects more than 1% of the human population. It has long been known that adenosine can reduce seizure generation in animal models of epilepsies. However, in addition to various side effects, the instability of adenosine has precluded its use as an anticonvulsant treatment. Here we report that a stable analogue of diadenosine-tetraphosphate: AppCH₂ppA effectively suppresses spontaneous epileptiform activity in vitro and in vivo in a Tuberous Sclerosis Complex (TSC) mouse model (Tsc1^+/−), and in postsurgery cortical samples from TSC human patients. These effects are mediated by enhanced adenosine signaling in the cortex post local neuronal adenosine release. The released adenosine induces A1 receptor-dependent activation of potassium channels thereby reducing neuronal excitability, temporal summation, and hypersynchronicity. AppCH₂ppA does not cause any disturbances of the main vital autonomous functions of Tsc1^+/− mice in vivo. Therefore, we propose this compound to be a potent new candidate for adenosine-related treatment strategies to suppress intractable epilepsies.

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Saccadic Adaptation Boosts Ongoing Gamma Activity in a Subsequent Visuoattentional Task

Abstract

Attention and saccadic adaptation (SA) are critical components of visual perception, the former enhancing sensory processing of selected objects, the latter maintaining the eye movements accuracy toward them. Recent studies propelled the hypothesis of a tight functional coupling between these mechanisms, possibly due to shared neural substrates. Here, we used magnetoencephalography to investigate for the first time the neurophysiological bases of this coupling and of SA per se. We compared visual discrimination performance of 12 healthy subjects before and after SA. Eye movements and magnetic signals were recorded continuously. Analyses focused on gamma band activity (GBA) during the pretarget period of the discrimination and the saccadic tasks. We found that GBA increases after SA. This increase was found in the right hemisphere for both postadaptation saccadic and discrimination tasks. For the latter, GBA also increased in the left hemisphere. We conclude that oculomotor plasticity involves GBA modulation within an extended neural network which persists after SA, suggesting a possible role of gamma oscillations in the coupling between SA and attention.

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Representing Multiple Observed Actions in the Motor System

Abstract

There is now converging evidence that others' actions are represented in the motor system. However, social cognition requires us to represent not only the actions but also the interactions of others. To do so, it is imperative that the motor system can represent multiple observed actions. The current fMRI study investigated whether this is possible by measuring brain activity from 29 participants while they observed 2 right hands performing sign language gestures. Three key results were obtained. First, brain activity in the premotor and parietal motor cortex was stronger when 2 hands performed 2 different gestures than when 1 hand performed a single gesture. Second, both individual observed gestures could be decoded from brain activity in the same 2 regions. Third, observing 2 different gestures compared with 2 identical gestures activated brain areas related to motor conflict, and this activity was correlated with parietal motor activity. Together, these results show that the motor system is able to represent multiple observed actions, and as such reveal a potential mechanism by which third-party social encounters could be processed in the brain.

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High Sensitivity Mapping of Cortical Dopamine D2 Receptor Expressing Neurons

Abstract

Cortical D2 dopamine receptor (Drd2) have mostly been examined in the context of cognitive function regulation and neurotransmission modulation of medial prefrontal cortex by principal neurons and parvalbumin positive, fast-spiking, interneurons in schizophrenia. Early studies suggested the presence of D2 receptors in several cortical areas, albeit with major technical limitations. We used combinations of transgenic reporter systems, recombinase activated viral vectors, quantitative translatome analysis, and high sensitivity in situ hybridization to identify D2 receptor expressing cells and establish a map of their respective projections. Our results identified previously uncharacterized clusters of D2 expressing neurons in limbic and sensory regions of the adult mouse brain cortex. Characterization of these clusters by translatome analysis and cell type specific labeling revealed highly heterogeneous expression of D2 receptors in principal neurons and various populations of interneurons across cortical areas. Transcript enrichment analysis also demonstrated variable levels of D2 receptor expression and several orphan G-protein-coupled receptors coexpression in different neuronal clusters, thus suggesting strategies for genetic and therapeutic targeting of D2 expressing neurons in specific cortical areas. These results pave the way for a thorough re-examination of cortical D2 receptor functions, which could provide information about neuronal circuits involved in psychotic and mood disorders.

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Early Adolescence is a Critical Period for the Maturation of Inhibitory Behavior

Abstract

Psychiatric conditions marked by impairments in cognitive control often emerge during adolescence, when the prefrontal cortex (PFC) and its inputs undergo structural and functional maturation and are vulnerable to disruption by external events. It is not known, however, whether there exists a specific temporal window within the broad range of adolescence when the development of PFC circuitry and its related behaviors are sensitive to disruption. Here we show, in male mice, that repeated exposure to amphetamine during early adolescence leads to impaired behavioral inhibition, aberrant PFC dopamine connectivity, and reduced PFC dopamine function in adulthood. Remarkably, these deficits are not observed following exposure to the exact same amphetamine regimen at later times. These findings demonstrate that there is a critical period for the disruption of the adolescent maturation of cognitive control and PFC dopamine function and suggest that early adolescence is particularly relevant to the emergence of psychopathology in humans.

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A rare case of large pyosalpinx in an elderly patient with well-controlled type 2 diabetes mellitus: a case report

Pyosalpinx, which is one of the pelvic inflammatory diseases, is usually observed in young women; it is rarely found in older women. Possible causative agents are thought to be Chlamydia trachomatis and Neisseria...

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Clinical inertia, reverse clinical inertia, and medication non-adherence in type 2 diabetes

Abstract

Purpose

Clinical inertia and medication non-adherence are thought to contribute largely to the suboptimal glycemic control in many patients with type 2 diabetes. The present review explores the relations between A1C targets, clinical inertia and medication non-adherence in type 2 diabetes.

Methods

We searched PubMed for English-language studies published from 2001 through June 1, 2018. We also manually searched the references of selected articles, reviews, meta-analyses, and practice guidelines. Selected articles were mutually agreed upon by the authors.

Results

Clinical inertia is the failure of clinicians to initiate or intensify therapy when indicated, while medication non-adherence is the failure of patients to start or continue therapy that a clinician has recommended. Although clinical inertia may occur at all stages of diabetes treatment, the longest delays were reported for initiation or intensification of insulin. Medication non-adherence to antidiabetic drugs may range from 53 to 65% at 1 year and may be responsible for uncontrolled A1C in about 23% of cases. Reverse clinical inertia can be acknowledged as the failure to reduce or change therapy when no longer needed or indicated. Clinical inertia and medication non-adherence are difficult to address: clinician-and patient-targeted educational programs, more connected communications between clinicians and patients, the help of other health professional figures (nurse, pharmacist) have been explored with mixed results.

Conclusions

Both clinical inertia and medication non-adherence remain significant barriers to optimal glycemic targets in type 2 diabetes. Moreover, part of clinical inertia may be a way through which clinicians face current uncertainty in medicine, including some dissonance among therapeutic guidelines. Scientific associations should find an agreement about how to measure and report clinical inertia in clinical practice and should exhort clinicians to consider reverse clinical inertia as a cause of persisting inappropriate therapy in vulnerable patients.

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Prevention of oral carcinogenesis in rats by Dracaena cinnabari resin extracts

Abstract

Objectives

In vivo study was performed to determine the chemopreventive efficacy of the DC resin methanol extract on a 4-nitroquinoline-1-oxide (4NQO) oral cancer animal model.

Materials and methods

This study involves administration of 4NQO solution for 8 weeks alone (cancer induction) or with Dracaena cinnabari (DC) extract at 100, 500, and 1000 mg/kg. DC extract administration started 1 week before exposure until 1 week after the carcinogen exposure was stopped. All rats were sacrificed after 22 weeks, and histological analysis was performed to assess any incidence of pathological changes. Immunohistochemical expressions of selected tumor marker antibodies were analyzed using an image analyzer computer system, and the expression of selected genes involved in apoptosis and proliferative mechanism related to oral cancer were evaluated using RT²-PCR.

Results

The incidence of OSCC decreased with the administration of DC extract at 100, 500, and 1000 mg/kg compared to the induced cancer group. The developed tumor was also observed to be smaller when compared to the induced cancer group. The DC 1000 mg/kg group inhibits the expression of Cyclin D1, Ki-67, Bcl-2, and p53 proteins. It was observed that DC 1000 mg/kg induced apoptosis by upregulation of Bax and Casp3 genes and downregulation of Tp53, Bcl-2, Cox-2, Cyclin D1, and EGFR genes when compared to the induced cancer group.

Conclusions

The data indicated that systemic administration of the DC resin methanol extract has anticarcinogenic potency on oral carcinogenesis.

Clinical relevance

Chemoprevention with DC resin methanol extract may significantly reduce morbidity and possibly mortality from OSCC.

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Transcriptome analysis reveals the molecular response to cadmium toxicity in P. pseudoannulata

Abstract

Cadmium (Cd) can be transferred and accumulated in spiders, posing a survival risk to them. To analyze potential biological damage caused by Cd accumulation and relevant detoxification strategies employed by spiders in response to Cd exposure, we conducted transcriptome analysis of the 5th instar spider P. pseudoannulata, a common spider species playing a vital role in natural pest control in agricultural fields of southern China. We obtained 92,778 unigenes with an average length of 1104 bp and identified 302, 655, and 424 differentially expressed genes (DEGs) in the spiders fed with Cd-containing fruit flies for 2, 5, and 8 days, respectively. Results showed that the body mass of Cd-containing P. pseudoannulata were reduced when compared with controls, presumably due to delayed maturation of tissues and organs. Meanwhile, functional analysis of DEGs indicated that Cd may have a negative effect on neural signal transduction and molt cycle of the spider. For defense strategies, detoxification enzymes like glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and P450, and typical proteins like heat shock protein and metallothionein were all differentially expressed in response to Cd stress. Besides, innate immune responses like toll-like receptor signaling pathways were also upregulated. Multiple critical Cd-responsive genes involved in biological damage, detoxification, and immune response were identified, providing referable foundation for further research on Cd toxicity to P. pseudoannulata.

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Synthesis of coal fly ash zeolite for the catalytic wet peroxide oxidation of Orange II

Abstract

Fly ash, a coal combustion residue produced by Termotasajero in Colombia, has been hydrothermally treated after an alkaline fusion to produce zeolite without addition of silicon or aluminum. The starting material was thoroughly mixed with NaOH, in a 1:1.2 mass ratio, to obtain a homogeneous mixture that was heated to 100 °C during different times (6, 8, and 10 h) and three zeolite samples were produced. The samples were characterized by XRD, SEM, XRF, Mössbauer spectroscopy, and N₂ physisorption. According to characterization results (high surface area and appropriate morphological properties including crystallinity) and synthesis time, zeolitic catalyst synthesized with 8 h of hydrothermal treatment was selected to perform further analysis. This sample consisted of a mixture of zeolite X and zeolite A of high surface area (301 m² g⁻¹) and a Fe content of 6% wt/wt. The zeolite was used as a catalyst for the Fenton oxidation of Orange II. Experiments were performed in a laboratory batch reactor at 70 °C and constant pH = 3, using different concentrations of H₂O₂. When the stoichiometric amount of H₂O₂ was used, good mineralization (X_TOC = 45%), complete discoloration, and oxidant consumption were obtained after 240 min of reaction. The sample retained activity after 16 h of usage. The presence of Fe in the reaction media was always detected and a homogeneous Fenton mechanism induced by surface-leached iron is suggested.

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Effectiveness of photopolymerization in composite resins using a novel 445-nm diode laser in comparison to LED and halogen bulb technology

Abstract

Challenges especially in the minimal invasive restorative treatment of teeth require further developments of composite polymerization techniques. These include, among others, the securing of a complete polymerization with moderate thermal stress for the pulp. The aim of this study is to compare current light curing sources with a blue diode laser regarding curing depth and heat generation during the polymerization process. A diode laser (445 nm), a LED, and a halogen lamp were used for polymerizing composite resins. The curing depth was determined according to the norm ISO 4049. Laser output powers of 0.1, 0.5, 1, and 2 W were chosen. The laser beam diameter was adapted to the glass rod of the LED and the halogen lamp (8 mm). The irradiation time was fixed at 40 s. To ascertain ΔT values, the surface and ground area temperatures of the cavities were simultaneously determined during the curing via a thermography camera and a thermocouple. The curing depths for the LED (3.3 mm), halogen lamp (3.1 mm) and laser_{(0.5/1 W)} (3/3.3 mm) showed no significant differences (p < 0.05). The values of ΔT_surface as well as ΔT_ground also showed no significant differences among LED, halogen lamp, and laser_{(1 W)}. The ΔT_surface values were 4.1_LED, 4.3_{halogen lamp}, and 4.5 °C for the laser while the ΔT_ground values were 2.7_LED, 2.6_{halogen lamp}, and 2.9 °C for the laser. The results indicate that the blue diode laser (445 nm) is a feasible alternative for photopolymerization of complex composite resin restorations in dentistry by the use of selected laser parameters.

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Phytochemical screening and antityrosinase activity of carvacrol, thymoquinone, and four essential oils of Lebanese plants

Journal of Cosmetic Dermatology, EarlyView.

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Phytochemical screening and antityrosinase activity of carvacrol, thymoquinone, and four essential oils of Lebanese plants

Journal of Cosmetic Dermatology, EarlyView.

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Effect of intermittent teriparatide (PTH 1-34) on the alveolar healing process in orchiectomized rats

Abstract

Objective

To evaluate intermittent teriparatide therapy's influence on the alveolar healing process in rats with induced osteoporosis.

Materials and methods

Fifty-four male rats were divided into three groups: fictitious surgery (SHAM), bilateral orchiectomy (ORQ NT), and bilateral orchiectomy treated with teriparatide (ORQ TERI). Right upper incisor extraction was performed. After 14 and 42 days, the rats were euthanized. Immunolabeling analysis was performed in order to characterize bone turnover through Wnt, alcaline phosphatase, osteocalcin, and TRAP presence in tissue; micro-CT analysis was performed in order to determine the bone volume fraction (BV/TV), trabecular thickness, separation, and number (Tb.Th, Tb.Sp, Tb.N). For the micro-CT data, statistical analysis was performed through one-way ANOVA and Tukey post-test, for parametrical data, with significance level adopted in p < 0.05. Days, Wnt, alkaline phosphatase, and osteocalcin revealed more labeling for ORQ TERI and less for TRAP. For the Tb.N in the ORQ NT group was 0.496 mm, a significant statistical difference was observed between the groups of ORQ NT and ORQ TERI (p < 0.05). For the BV/TV, Tb.Sp, and Tb.Th parameters, no significant statistical difference was observed among the three experimental groups (p > 0.05).

Conclusions

Treatment with intermittent teriparatide reverted impairment in the metabolism of repairing bone tissue in orchiectomized animals.

Clinical relevance

Cases of decreased bone density such as osteoporosis can lead to delayed alveolar repair process. PTH 1-34 has been shown to be a medication that improves this repair, making bone of low quality into one with normal features.

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Removal of vanadium and palladium ions by adsorption onto magnetic chitosan nanoparticles

Abstract

Chitosan (CS), synthesized from chitin chemically extracted from shrimp shells, was used for the synthesis of magnetic chitosan nanoparticles (Fe₃O₄-CSN), which makes the adsorbent easier to separate. Fe₃O₄-CSN was used for the removal of toxic metals such as vanadium (V(V)) and palladium (Pd(II)) ions from aqueous solutions. Influencing factors on the adsorption process such as pH, contact time, adsorbent dosage, and agitation speed were investigated. A competitive adsorption of V(V) and Pd(II) ions for the active sites was also studied. The monolayer maximum adsorption capacities (Q_m) of 186.6 and 192.3 mg/g were obtained for V(V) and Pd(II) ions, respectively. The pseudo-second-order equation gave the best fit for the kinetic data, implying that chemisorption was the determining step. Freundlich model yielded a much better fit than the other adsorption models assessed (Langmuir, Temkin and Dubinin-Radushkevich). Thus, the adsorption of V(V) and Pd(II) ions onto Fe₃O₄-CSN is a combination of physical and chemical adsorption, as based on the kinetics and equilibrium study. Generally, physical adsorption is the mechanism that governs the system, while chemical adsorption is the slowest adsorption step that takes place. Thermodynamic studies displayed that the adsorption process was exothermic and spontaneous. Removal efficiencies of 99.9% for V(V) and 92.3% for Pd(II) ions were achieved, implying that Fe₃O₄-CSN adsorbent had an excellent ability for the removal of the metal ions from real industrial wastewaters without remarkable matrix effect.

Graphical abstract

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Letter to the editor re: Cheng, YH., Chou, WC., Yang, YF. et al. Environ Sci Pollut Res (2017). https://ift.tt/2zUNieZ

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Silver and gold nanoparticles biosynthesized by aqueous extract of burdock root, Arctium lappa as antimicrobial agent and catalyst for degradation of pollutants

Abstract

This study presents an efficient and facile method for biosynthesis of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) using aqueous extract of burdock root (BR), A. lappa, and their applications. The nanoparticles were characterized by ultraviolet-visible spectrophotometry, X-ray diffraction, transmission electron microscopy, energy dispersive X-ray, thermogravimetry, and differential thermal analysis. AgNPs capped the BR extract (BR-AgNPs) possessed roughly spherical geometry with an average diameter of 21.3 nm while uneven geometry of AuNPs capped the BR extract (BR-AuNPs) showed multi shapes in average size of 24.7 nm. The BR-AgNPs strongly inhibited five tested microorganism strains. In particular, the nanoparticles showed excellent catalytic activity for the conversion of pollutants within wastewater. Pseudo-first-order rate constants for the degradation of 4-nitrophenol, methyl orange, and rhodamine B were respectively found 6.77 × 10⁻³, 3.70 × 10⁻³, and 6.07 × 10⁻³ s⁻¹ for BR-AgNPs and 6.87 × 10⁻³, 6.07 × 10⁻³, and 7.07 × 10⁻³ s⁻¹ for BR-AuNPs.

Graphical abstract

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A response surface methodology for optimization of 2,4-dichlorophenoxyacetic acid removal from synthetic and drainage water: a comparative study

Abstract

The potential of a granular activated carbon (GAC), a rice husk biochar (BRH), and multi-walled carbon nanotubes (MWCNTs) for removing 2,4-dichlorophenoxyacetic acid (2,4-D) from simulated wastewater and drainage water has been evaluated. In this regard, a response surface methodology (RSM) with a central composite design (CCD) (CCD-RSM design) was used to optimize the removal of 2,4-D from simulated wastewater under different operational parameters. The maximum adsorption capacities followed the order GAC > BRH > MWCNTs, whereas the equilibrium time increased in the order MWCNTs < GAC < BRH. In the case of GAC and BRH, the 2,4-D removal percentage increased significantly upon increasing the adsorbent dosage and temperature and decreased upon increasing the initial 2,4-D concentration and pH. The results showed that the contact time and temperature were not important as regards the adsorption efficiency of 2,4-D by MWCNTs, whereas rapid removal of 2,4-D from simulated wastewater was achieved within the first 5 min of contact with the MWCNTs. The results confirmed that the Freundlich isotherm model with the highest coefficient of determination (R²) and the lowest standard error of the estimate (SEE) satisfactorily fitted the 2,4-D experimental data. In addition, successful usage of the three adsorbents investigated was observed for removal of 2,4-D from drainage water from an agricultural drainage system. An economic analysis with a rate of return (ROR) method indicated that BRH could be used as an eco-friendly, low-cost, versatile, and high adsorption capacity alternative to GAC and MWCNTs for the removal of 2,4-D.

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Coffee waste, vector control, and dengue

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Natural regulatory plasma cells

Simon Fillatreau

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Photobiomodulation on critical bone defects of rat calvaria: a systematic review

Abstract

Bone defects following trauma represent a high impact on the quality of life of millions of people around the world. The aim of this study was to review photobiomodulation (PBM) action in the treatment of bone critical defects in rat calvaria, related to evaluation of the current protocols applied. One hundred and forty-seven articles related to the subject were found by searching the main databases (Pubmed, Lilacs, Web of Science, and Scopus) considering the period of publication until the year 2017, and only 14 corresponded the inclusion criteria established for this systematic review. The main parameters of the PBM were expressed in Table 1. In addition, it was possible to observe the use of two different wavelengths (red and infrared), which are considered therapeutic. Most of the evaluated articles presented positive results that describe a greater amount of neoformed bone, an increase in collagen synthesis, and a contribution to microvascular reestablishment. However, two studies report no effect on the repair process when the PBM was used. In addition, we observed considerable variations between the values of power, fluence, and total energy, which make it difficult to compare the results presented between the selected studies. It was possible to conclude that the infrared laser was more effective in positively stimulating the bone repair process of critical defects. Furthermore, a discrepancy was found in the parameter values used, which made it difficult to choose the best protocol for the treatment of this type of lesion.

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Genotoxicity of water samples from an area of the Pampean region (Argentina) impacted by agricultural and livestock activities

Abstract

The aim of this study was to assess the genotoxic potential of surface waters located in a rural area in the north east of Buenos Aires province (Argentina) using the Allium cepa test. Water samples were collected at four sites located in a drainage channel and two sites on the Burgos stream that receives water from the channel, taking into account the sowing and harvesting months and rainfall periods. Analytical determinations revealed high total concentrations of Cd, Cu, Pb, and Zn (maximum values: 0.030, 0.252, 0.176, and 0.960 mg L⁻¹, respectively), and concentrations of glyphosate and its metabolite aminomethylphosphonic acid (AMPA), with maximum values of 13.6 and 9.75 μg L⁻¹, respectively. Statistically positive correlations were observed between the total metal concentrations and precipitation. No cytotoxicity (mitotic index MI) was observed in A. cepa. However, several water samples showed significant increases in micronucleus (MN) frequencies with respect to the controls. No correlations were observed between MN and the abiotic variables or precipitation. These results showed a state of deterioration in the water quality at the rural area studied in Buenos Aires province, and heavy metal contamination may contribute to the genotoxic activity. A. cepa was shown to be a useful tool for the detection of genotoxicity in water samples from areas with agricultural and livestock activities.

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Study on dynamic adsorption of p-nitrophenol by multi-walled carbon nanotubes dispersed cyclodextrin

Abstract

In this paper, the modified multi-walled carbon nanotubes were prepared by β-cyclodextrin denoted as β-CD-MWNTs. The structure and morphology of β-CD-MWNTs was characterized by TEM and the dynamic adsorption of p-nitrophenol on β-CD-MWNTs was studied by the Thomas model. Some affecting factors of dynamic adsorption and the adsorbent regeneration process such as the sewage concentration, the amount of absorbent in column, including the type of reagent, solid-liquid ratio, regeneration time, and regeneration times were investigated and optimized. The results indicated that the p-nitrophenol removal rate could reach 84% under stuffing 2 g β-CD-MWNTs. The curves of p-nitrophenol's dynamic adsorption conformed to the Thomas model. Moreover, the adsorption capacity of regenerated β-CD-MWNTs was similar to the fresh β-CD-MWNT column. The optimal conditions of regenerations of β-CD-MWNTs were shown as follows: the type of reagent is anhydrous ethanol, the solid-liquid ratio is 200:40 (mg/mL) and the regeneration time is 120 min.

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To treat or not to treat: The minimally symptomatic EoE patient

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder in which a mixed inflammatory cell infiltrate leads to symptoms of esophageal dysfunction. While great strides have been made to understand the pathophysiology and natural history of eosinophilic esophagitis over the last 30 years, there still does not exist an FDA-approved therapy.

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Metabotropic glutamate receptor subtype 5 is altered in LPS-induced murine neuroinflammation model and in the brains of AD and ALS patients

Abstract

Purpose

The aim of the present study was to determine the expression levels of mGluR5 in different mouse strains after induction of neuroinflammation by lipopolysaccharide (LPS) challenge and in the brains of patients with Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) post mortem to investigate mGluR5 expression in human neurodegenerative diseases.

Methods

C57BL/6 and CD1 mice were injected intraperitoneally with either 10 mg/kg LPS or saline. mGluR5 and TSPO mRNA levels were measured after 1 and 5 days by qPCR, and mGluR5 protein levels were determined by PET imaging with the mGluR5-specific radiotracer [¹⁸F]PSS232. mGluR5 expression was evaluated in the post-mortem brain slices from AD and ALS patients using in vitro autoradiography.

Results

mGluR5 and TSPO mRNA levels were increased in brains of C57BL/6 and CD1 mice 1 day after LPS treatment and remained significantly increased after 5 days in C57BL/6 mice but not in CD1 mice. Brain PET imaging with [¹⁸F]PSS232 confirmed increased mGluR5 levels in the brains of both mouse strains 1 day after LPS treatment. After 5 days, mGluR5 levels in CD1 mice declined to the levels in vehicle-treated mice but remained high in C57BL/6 mice. Autoradiograms revealed a severalfold higher binding of [¹⁸F]PSS232 in post-mortem brain slices from AD and ALS patients compared with the binding in control brains.

Conclusion

LPS-induced neuroinflammation increased mGluR5 levels in mouse brain and is dependent on the mouse strain and time after LPS treatment. mGluR5 levels were also increased in human AD and ALS brains in vitro. PET imaging of mGluR5 levels could potentially be used to diagnose and monitor therapy outcomes in patients with AD and ALS.

https://ift.tt/2pFbso4

Multidisciplinary Tracheostomy Care

There have been reports of successful quality-improvement initiatives surrounding tracheostomy care for more than a decade, but widespread adoption of best practices has not been universal. Five key drivers have been found to improve the quality of care for tracheostomy patients: multidisciplinary synchronous ward rounds, standardization of care protocols, appropriate interdisciplinary education and staff allocation, patient and family involvement, and use of data to drive improvement. The Global Tracheostomy Collaborative is a quality-improvement collaborative dedicated to improving the care of tracheostomy patients worldwide through communication, dissemination, and implementation of proven strategies based on these 5 key drivers.

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Publicly Available Databases in Otolaryngology Quality Improvement

The historical context for quality improvement is provided. Important differences are described between the two overarching types of databases: clinical registries and administrative databases. The pros and cons of each are provided as are examples of their utilization in otolaryngology–head and neck surgery.

https://ift.tt/2Qx9yRJ

Management of Flaccid Facial Paralysis of Less Than Two Years’ Duration

Flaccid facial paralysis results in disfiguring facial changes. The treatment of flaccid facial paralysis is complex and treatment approaches should be determined based on duration and the causes of paralysis, status and accessibility of the affected facial nerve, medical comorbidities, and patient-specific goals. Although primary nerve repair is the preferred treatment strategy when possible, nerve substitution procedures are the mainstay of treatment for patients with flaccid facial paralysis of less than 2 years duration.

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Delivering Otolaryngologic Care Safely and Successfully

In 2000, when the Institute of Medicine published To Err Is Human,1 the focus of the patient safety movement was on convincing both providers and patients that we had a safety problem. Currently, most people understand that patient safety is a real issue. Unfortunately, there are still an estimated 251,000 deaths2 and over 1,000,000 nonfatal injuries3 from medical errors annually in the United States. The focus now is on how to implement the best practices that we know exist. An additional challenge is creating a culture around safety, with leadership engagement.

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The use of topical rapamycin in the treatment of superficial lymphatic malformations

Rapamycin can be useful in the treatment of vascular malformations, but the value of its topical application to superficial lymphatic malformations has not been established .Topical rapamycin improves the clinical appearance of superficial lymphatic malformations and alleviates associated symptoms.  

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Approaches to limit systemic antibiotic use in acne: Systemic alternatives, emerging topical therapies, dietary modification, and laser and light-based treatments

Acne is one of the most common diseases worldwide and affects approximately 50 million individuals in the United States. Oral antibiotics are the most common systemic agent prescribed for the treatment of acne. However, their use may be associated with a variety of adverse outcomes including bacterial resistance and disruption of the microbiome. As a result, multiple treatment guidelines call for limiting the use of oral antibiotics in the treatment of acne, although actual prescribing often does not follow these guidelines.

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Surgical Pearl: Achieving Eversion Utilizing Topical Tissue Adhesive

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Predictors of mucosal melanoma survival in a population-based setting

This population-based study underscores that extracutaneous melanomas are rare and aggressive neoplasms. Poorer survival in patients with mucosal melanoma was observed in relation to stage and anatomic site, but not tumor thickness (i.e., Breslow depth) or patient race/ethnicity. Due to the poor prognosis for all stages of mucosal melanoma, dermatologists should consider incorporating examination of the oropharynx and genitalia in the full body skin exam.

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Dipeptidyl-peptidase IV inhibitor-associated bullous pemphigoid: A systematic review and meta-analysis

https://ift.tt/2pB4ala

Relative efficacy of systemic treatments for atopic dermatitis

Systemic treatments are common for severe atopic dermatitis and biologic medications represent recent advances in the field. Dupilumab and cyclosporine are both effective at improving clinical severity of atopic dermatitis, as are newer biologic medications lebrikizumab and tralokinumab. Long term efficacy and safety results are needed for biologic medications.

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Comparative Clinicopathological Analysis of Cutaneous Peripheral T-cell lymphoma, Not Otherwise Specified, According to Primary Tumor Site

https://ift.tt/2pBZYBx

Future considerations for clinical dermatology in the setting of 21st century American policy reform: corporatization and the rise of private equity in dermatology

Within the last two decades, for-profit financial groups have become increasingly involved in health care. Outlier dermatology practices with high volumes of well-reimbursed procedures are attractive to consolidation backed by private equity. With fewer choices for independent or group private practice, junior dermatologists are increasingly seeking employment without ownership in private equity-backed corporate groups, whose primary fiscal responsibility lies with investors. Medicare's response to corporatization and consolidation has already changed the practice of dermatopathology.

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Co-occurrence of infantile hemangiomas and other birthmarks

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Analysis of cutaneous Merkel Cell Carcinoma outcomes after different surgical interventions

Despite current recommendation of 1-2 cm excision margin for merkel cell carcinoma, we compared different surgical option for better outcome. We did not recommend local destruction and confirmed superior survival with excision margin of more than 2 cm in patients younger than 60 years having T1/T2 tumors or adjuvant radiotherapy.

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Characteristics, treatment and outcome of bleeding after tooth extraction in patients on DOAC and phenprocoumon compared to non-anticoagulated patients—a retrospective study of emergency department consultations

Abstract

Objectives

Bleeding after tooth extraction range from minor bleeding to life-threating haemorrhagic shock and are among the leading complications in patients under oral anticoagulation with direct oral anticoagulants (DOACs) or phenprocoumon. Little is known about how anticoagulation in patients under DOAC or phenprocoumon alters the characteristics, treatment or outcome of bleeding events, in comparison to non-anticoagulated patients.

Methods

Patients admitted to a tertiary ED in Bern, Switzerland, from June 1st 2012 to 31st May 2016 with bleeding related to tooth extraction under DOAC, phenprocoumon or without anticoagulation, were compared.

Results

Out of 161,458 emergency consultations, 64 patients with bleeding from tooth extraction were included in our study. In anticoagulation groups, we found significantly more delayed bleeding events than in patients without anticoagulation (9 (81.3%) DOAC, 19 (86.4%) phenprocoumon, 8 (30.8%) no anticoagulation, p < 0.001). Anticoagulated patients had to stay longer in the ED than non-anticoagulated patients, with no significant difference between DOAC or phenprocoumon (hours: 4.8 (3.2–7.6 IQR) DOAC, 3.0 (2.0–5.5 IQR) phenprocoumon, p = 0.133; 2.7 (1.6–4.6) no anticoagulation; p = 0.039). More patients with anticoagulation therapy needed surgery than patients without anticoagulant therapy (11 (68.8%) DOAC, 12 (54.6%) VKA, p = 0.506; 7(26.9%) no anticoagulation; p = 0.020).

Conclusions

Delayed bleeding occur more often in anticoagulated patients with both DOAC and phenprocoumon compared to patients without anticoagulation. Bleeding events in anticoagulated patients with DOAC and phenprocoumon equally need longer ED treatment and more frequent surgical intervention.

Clinical relevance

Caution with delayed bleeding in anticoagulated patients with DOACs and phenprocoumon is necessary and treatment of bleeding is resource-demanding.

https://ift.tt/2E2uNJP

FDG PET/CT for assessing tumour response to immunotherapy

Abstract

This paper follows the immunotherapy symposium held during the European Association of Nuclear Medicine (EANM) 2017 Annual Congress. The biological basis of the immune checkpoint inhibitors and the drugs most frequently used for the treatment of solid tumours are reviewed. The issues of pseudoprogression (frequency, timeline), hyperprogression and immune-related side effects are discussed, as well as their implications for patient management. A review of the recent literature on the use of FDG PET for assessment of immunotherapy is presented, and recommendations are provided for assessing tumour response and reporting immune-related side effects with FDG PET based on published data and experts' experience. Representative clinical cases are also discussed.

https://ift.tt/2OaHvuw

Magnesium depletion suppresses the anti-grazer colony formation in Scenedesmus obliquus

Abstract

In aquatic ecosystems, many phytoplankton species have evolved various inducible defense mechanisms against the predation. The expression of these defenses is affected by environmental conditions such as nutrient availability. Here, we investigated the anti-grazer colony formation in Scenedesmus obliquus at different magnesium concentrations (0–7.3 mg L⁻¹ Mg²⁺) in the presence of zooplankton (Daphnia)-derived infochemicals. Results showed that at adequate Mg²⁺, S. obliquus formed high proportions of multi-celled (e.g., four- and eight-celled) colonies, resulting in significantly increased number of cells per colony in response to Daphnia filtrate. On the other hand, in Mg²⁺-deficient treatment, the proportion of multi-celled colonies decreased, together with reduced algal growth rate and photosynthetic efficiency. Finally, the treatment without Mg²⁺ strongly suppressed the formation of large colony (mainly eight-celled colonies), whereas the algal growth rate was comparable to that in Mg²⁺ sufficient treatment. Despite the inhibition of colony formation, the time reaching the maximum number of cells per colony was not affected by the Mg²⁺ concentration, which generally took three days in all groups. Our results indicate that Mg²⁺ deficient/absent environments significantly reduced anti-grazing colony formation but not the algal growth, suggesting strong dependability of this morphological defensive trait to magnesium fluctuation in S. obliquus.

https://ift.tt/2BZgO4T

An event study analysis of price adjustment of refined oil and air quality in China

Abstract

Since marketization of the refined oil price, the Chinese government has used refined oil price adjustments to control air pollution. Using an event study analysis, we examine whether these price adjustments have impacted air quality. We test the abnormal returns of 12 price adjustments between 2014 and 2015 in 51 major cities of China. The results show that the impact on air quality of refined oil price decreases is larger than the impact of oil price increases. Although results indicate air quality has deteriorated, the impact is insignificant for most of the cities. Consequently, we conclude that price suspension of refined oil has had a negligible impact on air quality. This policy is not a viable method to improve the air quality in the short run.

https://ift.tt/2Cxr718

Chitosan oligosaccharides alleviate PM 2.5 -induced lung inflammation in rats

Abstract

Air pollution of particulate matter (PM), especially PM_2.5, has become a major public health problem in China. Exploration of therapeutic and preventive measures against PM_2.5 toxicity is of practical significance. The aim of this study was to examine the inhibitory effects of chitosan oligosaccharides (COS) on PM_2.5-induced lung inflammation in rats. Forty SPF (specific pathogen-free) male Wistar rats weighing 200–220 g were randomly divided into four groups: control group, COS group, PM_2.5 group, and PM_2.5+COS group. COS was pre-administered to rats by gavage at a single dose of 500 mg/kg 2 h before intratracheal instillation of PM_2.5 at a single dose of 1.2 mg/kg daily for 3 consecutive days. Normal saline (NS) was used as negative control. Twenty-four hours after the last instillation of PM_2.5, rats were sacrificed and subjected to bronchoalveolar lavage (BAL). The BAL fluids (BALF) were collected for measurement of levels of total proteins, lactate dehydrogenase (LDH), interleukin-1 (IL-1β), IL-8, and tumor necrosis factor-ɑ (TNF-ɑ) using colorimetric or ELISA kits. Levels of total proteins, LDH activities, and pro-inflammatory mediators including IL-1β, IL-8, and TNF-ɑ in BALF of rats in PM_2.5 group significantly increased in comparison with those of the control group. Pre-treatment of rats with COS markedly blocked PM_2.5-induced increase in LDH, IL-8, and TNF-ɑ levels in BALF. In conclusion, PM_2.5 exposure induces rat lung inflammation, which could be ameliorated by the pre-treatment of COS.

https://ift.tt/2BYbCy9

To treat or not to treat: The minimally symptomatic EoE patient

Publication date: Available online 5 October 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Amanda Muir, Hillary Moore, Jonathan Spergel

https://ift.tt/2PfBOrI

Lupin: An Emerging Food Allergen in the United States

Publication date: Available online 4 October 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Theresa A. Bingemann, Carah B. Santos, Anne F. Russell, Aikaterini Anagnostou

https://ift.tt/2y3NhUT

Sensitization Profiles to Hazelnut Allergens across the United States of America

Publication date: Available online 4 October 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Andre Valcour, Jonas Lidholm, Magnus P. Borres, Robert G. Hamilton

https://ift.tt/2QxlEKx

Level of competence of primary and secondary school teachers in the management of anaphylaxis

Publication date: Available online 4 October 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Silvia F Cantariño, Silvia Novío

https://ift.tt/2zUjj77

Ultrasound-guided quadratus lumborum block in pediatrics: trans-muscular versus intra-muscular approach

Abstract

Purpose

Quadratus lumborum (QL) block has four approaches. However, there is difference between the four approaches regarding efficacy, safety and adverse effects. The primary objective of this study is to compare the analgesic effect between trans-muscular and intra-muscular approaches of the QL block in pediatric patients for elective lower abdominal surgery.

Methods

54 patients aged between 1 and 6 years were enrolled. Patients of both genders were selected. The patients were randomly classified into two groups: Group TQL includes patients (27 patients) in whom bilateral QL block was performed using trans-muscular approach, and Group IQL (27 patients), which underwent bilateral QL block using an intra-muscular approach. The primary outcome measure was the number of patients who require rescue analgesia in the first 24 h. The secondary outcome measures were FLACC score, heart rate, non-invasive blood pressure at 2, 4, 6, 12, and 24 h postoperatively, and postoperative complications (e.g., quadriceps muscle weakness, local hematoma).

Results

In the first 24 h after surgery, 13 patients in the IQL group (48.1%) required rescue analgesia, whereas only five patients in the TQL group (18.5%) required rescue analgesia. The FLACC score was lower in the TQL group than the IQL group at all time intervals up to 24 h postoperatively. In the TQL group, eight patients (29.6%) developed quadriceps weakness; whereas, only one patient (3.7%) in the IQL group developed quadriceps weakness.

Conclusion

TQL is better than IQL in the analgesic efficacy following the pediatric lower laparotomy.

https://ift.tt/2pzwioS

Atopic dermatitis in cats and dogs: a difficult disease for animals and owners

The purpose of this review article is to give an overview of atopic dermatitis in companion animals and of recent developments including knowledge on immunological background, novel treatment options and diffi...

https://ift.tt/2RtcJew

Intact Automatic Motor Inhibition in Attention Deficit Hyperactivity Disorder

Publication date: Available online 5 October 2018

Source: Cortex

Author(s): Marius Keute, Kerstin Krauel, Hans-Jochen Heinze, Max-Philipp Stenner

Abstract

Hyperactivity and impulsivity are defining symptoms of attention-deficit hyperactivity disorder (ADHD), next to inattention. Hyperactive and impulsive behavior in ADHD is often thought to result from a deficit in inhibitory motor control. However, testing for such a deficit is complicated by coexisting deficits in ADHD, specifically an impairment in maintaining task set, e.g., due to inattention. Typical inhibition paradigms, such as Stop-signal, Go/NoGo or Flanker paradigms, are susceptible to a fundamental confound between inhibition and inattention because inhibition is an explicit goal in these tasks. We eliminate this confound by studying the negative compatibility effect (NCE), reflecting a core inhibitory function in the human motor system which, in healthy individuals, inhibits movements automatically, i.e., without deliberation or even conscious awareness. Our behavioral analysis, including Bayesian model comparison, as well as the time-course of the lateralized readiness potential (LRP), consistently show that this function is intact in children with ADHD compared to healthy controls, independent of the presence or absence of prominent hyperactive-impulsive symptoms. We conclude that hyperactivity and impulsivity in ADHD do not result from a low-level deficit in motor inhibition.

https://ift.tt/2IF4h81

Evolutionary divergence of neuroanatomical organization and related genes in chimpanzees and bonobos

Publication date: Available online 5 October 2018

Source: Cortex

Author(s): Nicky Staes, Jeroen B. Smaers, Amanda E. Kunkle, William D. Hopkins, Brenda J. Bradley, Chet C. Sherwood

Abstract

Given their close genetic relatedness to humans, bonobos (Pan paniscus) and chimpanzees (Pan troglodytes) offer an essential comparative framework for studying the evolution of uniquely human traits. These two species differ markedly in their socio-behavioral repertoires, which is reflected in neuroanatomical differences that have been reported in the literature. However, phylogenetic comparative methods have not yet been used to map the evolution of neuroanatomical traits in bonobos and chimpanzees, limiting our ability to understand which neural systems are derived in each species in relation to the last common ancestor of Pan (Pan-LCA). Here, we examine evolutionary changes in neuroanatomical traits of bonobos and chimpanzees relative to ancestral character reconstructions of the Pan-LCA using comparative datasets from hominoids. We found that bonobo brains are derived in showing reduction of whole brain and white matter volumes, with particularly striking reduction of male brain size compared to the inferred Pan-LCA value. Brain structures related to social cognition and emotional regulation, like the insular cortex and amygdala, display a mosaic pattern of evolution with certain traits changing to a greater extent in each species. Examination of potential genetic mechanisms underlying divergence of neural and social traits did not reveal clear differences in protein evolution patterns between the two species. These findings suggest that the brain anatomy of extant bonobos and chimpanzees show lineage-specific specializations and neither can be considered to more closely retain the ancestral state of Pan. Consequently, this raises questions about the extent that modern chimpanzees or bonobos may serve as referential models for the neuroanatomy of the LCA of humans and apes.

https://ift.tt/2OL4kot

The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial

Publication date: Available online 4 October 2018

Source: Cortex

Author(s): Miranka Wirth, Gloria Benson, Claudia Schwarz, Theresa Köbe, Ulrike Grittner, Dietmar Schmitz, Stephan J. Sigrist, Jens Bohlken, Slaven Stekovic, Frank Madeo, Agnes Flöel

Abstract

Introduction

Nutritional intervention with the natural polyamine spermidine, an autophagy-enhancing agent, can prevent memory loss in aging model organisms. This is the first human study to evaluate the impact of spermidine supplementation on memory performance in older adults at risk for the development of Alzheimer's disease.

Methods

Participants with subjective cognitive decline (n = 30) were included in this three-months, randomized, placebo-controlled, double-blind Phase IIa pilot trial with a spermidine-rich plant extract supplement. Effects of intervention were assessed using the behavioral mnemonic similarity task at baseline and post-intervention visits. Data analysis was focused on reporting and interpreting effectiveness based on effect sizes.

Results

Memory performance was moderately enhanced in the spermidine group compared with placebo at the end of intervention (contrast mean = 0.17, 95% confidence interval [CI]: -0.01, 0.35, Cohen's d = 0.77, 95% CI: 0, 1.53). Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean difference = -0.11, 95% CI: -0.19, -0.03, Cohen's d = 0.79, 95% CI: 0.01, 1.55). A similar effect was not found in the placebo-treated group (mean difference = 0.07, 95% CI: -0.13, 0.27, Cohen's d = -0.20, 95% CI: -0.94, 0.54).

Discussion

Nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. This beneficial effect might be mediated by stimulation of neuromodulatory actions in the memory system. A follow-up Phase IIb randomized controlled trial will help validate the therapeutic potential of spermidine supplementation and delineate possible neurophysiological mechanisms of action in the target population.

Trial registration

Registered in ClinicalTrials.gov with the Identifier NCT02755246.

https://ift.tt/2BYmFY3

Oculomotor capture reveals trial-by-trial neural correlates of attentional guidance by contents of visual working memory

Publication date: Available online 4 October 2018

Source: Cortex

Author(s): Valerie M. Beck, Timothy J. Vickery

Abstract

Evidence from attentional and oculomotor capture, contingent capture, and other paradigms suggests that mechanisms supporting human visual working memory (VWM) and visual attention are intertwined. Features held in VWM bias guidance toward matching items even when those features are task irrelevant. However, the neural basis of this interaction is underspecified. Prior examinations using fMRI have primarily relied on coarse comparisons across experimental conditions that produce varying amounts of capture. To examine the neural dynamics of attentional capture on a trial-by-trial basis, we applied an oculomotor paradigm that produced discrete measures of capture. On each trial, subjects were shown a memory item, followed by a blank retention interval, then a saccade target that appeared to the left or right. On some trials, an irrelevant distractor appeared above or below fixation. Once the saccade target was fixated, subjects completed a forced-choice memory test. Critically, either the target or distractor could match the feature held in VWM. Although task irrelevant, this manipulation produced differences in behavior: participants were more likely to saccade first to an irrelevant VWM-matching distractor compared with a non-matching distractor – providing a discrete measure of capture. We replicated this finding while recording eye movements and scanning participants' brains using fMRI. To examine the neural basis of oculomotor capture, we separately modeled the retention interval for capture and non-capture trials within the distractor-match condition. We found that frontal activity, including anterior cingulate cortex and superior frontal gyrus regions, differentially predicted subsequent oculomotor capture by a memory-matching distractor. Other regions previously implicated as involved in attentional capture by VWM-matching items showed no differential activity across capture and non-capture trials, even at a liberal threshold. Our findings demonstrate the power of trial-by-trial analyses of oculomotor capture as a means to examine the underlying relationship between VWM and attentional guidance systems.

https://ift.tt/2OBJVly

CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients

Abstract

Endolymphatic sac tumors (ELSTs) are rare, slowly growing temporal bone neoplasms which show a high association with von Hippel-Lindau (VHL) syndrome. The immunohistochemistry evaluation of these papillary-cystic neoplasms frequently raises the differential diagnosis with renal cell carcinoma, among other metastatic neoplasms, whether in VHL patients or not. A cohort of 26 patients with ELSTs were evaluated for histologic features, immunohistochemistry findings, and association with VHL. Standard immunohistochemistry evaluation was performed. Sixteen females and 10 males ranging in age from 10 to 69 years (mean 44; VHL mean: 32) at initial presentation, comprised the cohort of patients. Most (86%) experienced hearing changes or inner ear symptoms (vertigo, dizziness), with an average duration of symptoms for 39 months (range 2–240 months). The tumors were an average of 2.9 cm (range 0.4–8 cm), with 14 left, 11 right sided and one bilateral tumor. Nine patients had documented VHL, with 3 patients having a concurrent or subsequent clear cell renal cell carcinoma. Patients were followed an average of 6.2 years (available in 24 patients): 19 alive without disease, 7.5 years; 2 dead without disease, 1.2 years; and 3 alive with disease, 3.1 years. The neoplastic cells show the following immunohistochemistry findings: AE1/AE3, EMA, CK7, CAIX, GLUT1, VEGF: 100% of cases tested were positive; pax-8: 85% of cases positive; CD10 and RCC: 0% of cases reactive. Based on this cohort of 26 patients with ELST, 9 of whom had VHL, the strong pax-8 and CAIX should be used in conjunction with negative CD10 and RCC to help exclude a metastatic renal cell carcinoma. As CAIX is an enzyme overexpressed in hypoxia and hypoxia inducible factor is what VHL protein regulates, this is an expected, although previously unreported finding. Whether part of VHL or not, VHL mutations may be a somatic rather than germline finding in the tumors, a possible further explanation for the CAIX reaction.

https://ift.tt/2yiefaH

Paediatric auditory brainstem implantation: The South Asian experience

Publication date: Available online 4 October 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): S. Raghunandhan, K. Madhav, A. Senthilvadivu, K. Natarajan, M. Kameswaran

Abstract

Introduction

Paediatric Auditory Brainstem Implantation (ABI) is indicated for children with congenital cochlear aplasia, absent/hypoplastic vestibulocochlear nerve, for whom cochlear implantation is not possible. Knowledge of the anatomical landmarks and variants in anatomy of the brainstem is vital for ABI surgery.

Method

Study was done at Auditory implant centre in Madras ENT research foundation, which includes 24 children who had undergone ABI surgery and are being followed up for 1 year, post operatively. Aims were to study the anatomical variants and the outcomes of ABI implantation. To determine if different anatomical variants effect placement of ABI electrode. To assess the patient outcomes by Categories of auditory Performance (CAP) scores and Speech Intelligibility Ratings (SIR) scores.

Results

All the candidates showed gradual improvement in audiological and verbal outcomes after the ABI. The mean CAP and SIR scores after 6 months of AVHT were 2.07 and 1.37 respectively. After 1 year of auditory verbal rehabilitation therapy CAP was 3.42 and SIR was 2.33. Flocculus of the cerebellum can be of different grades. Though, there was difficulty in insertion of the electrode in subjects with anatomical variants, the outcomes were comparable with other subjects.

Conclusion

ABI surgery involves frequent anatomical variations surrounding the lateral recess which makes the positioning of the auditory prosthesis difficult. Variants during the surgery can make the placement of ABI electrodes difficult, but promising results were seen all the implantees.

https://ift.tt/2QxdH8l

Strategy for facial nerve management during surgical removal of benign jugular foramen tumors: Outcomes and indications

Publication date: Available online 4 October 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): J.-Q. Chen, H.-Y. Tan, Z.-Y. Wang, W.-D. Zhu, Y.-C. Chai, H. Jia, H. Wu

Abstract

Objective

Classical surgical management of jugular foramen (JF) tumors usually requires facial nerve rerouting which results in permanent facial palsy in most patients. The purpose of the article is to study the outcomes of different rerouting techniques, and to discuss their indications.

Material and methods

We retrospectively reviewed 98 patients with JF tumors operated at our center between January 2008 and December 2016 using different surgical approaches with the following procedures for facial nerve management: total anterior rerouting (TR), partial anterior rerouting (PR), and fallopian bridge (FB) technique. The data for facial nerve management, surgical outcome and postoperative facial nerve function were collected from the medical records.

Results

In the study, there were 48 males and 50 females. Of them, 61 (62.2%) were jugular paragangliomas, 22 (22.4%) schwannomas, and 15 (15.3%) meningiomas. Total tumor removal was achieved in 95 (96.9%) patients, while near-total removal was achieved in 3 (3.1%) paragangliomas. TR was applied in 31 (31.6%) patients with PR in 26 (26.5%) patients, and FB in 41 (41.8%) patients. The mean follow-up duration was 39.4 ± 22.6 months, and 2 recurrences of paragangliomas were observed. Seventy-five patients (76.5%) had good facial function (HB I-II) at 1 year after surgery, the patients who received a TR approach presented significantly less HB I-II FN function (48.4%) than those with PR (82.6%, P < 0.05) or those with FB technique (95.1%, P < 0.001). 21 patients (21.4%) presented new-onset lower cranial nerve dysfunction of which 13 recovered at 1 year after surgery.

Conclusion

Facial nerve management in JF tumors should be tailored individually. No-rerouting methods, such as the fallopian bridge technique, bring significantly better results in terms of facial nerve function, which might be performed first during surgery; its indication is based mainly on the tumor type and extent.

https://ift.tt/2zT9oyK

CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients

Abstract

https://ift.tt/2yiefaH

CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients

Abstract

https://ift.tt/2yiefaH

The epigenetic landscape in the cardiovascular complications of diabetes

Abstract

A growing body of evidence suggests that epigenetic modifications—changes to the genome that do not involve changes in DNA sequence—may significantly derail transcriptional programs implicated in angiogenesis, oxidative stress and inflammation, thus fostering cardiovascular damage in patients with diabetes. Notably, adverse epigenetic signals acquired over the life course can be transmitted to the offspring, and may contribute to early cardiovascular phenotypes in the young generations. Hyperglycaemia and insulin resistance—key hallmarks of diabetes—induce an array of epigenetic modifications (i.e., DNA methylation, histone marks, and non-coding RNAs) which are responsible for a long-lasting impairment of vascular and cardiac function, even after intensive glycemic control. Hence, unveiling the "epigenetic landscape" in patients with diabetes may provide a post-genomic snapshot of global cardiovascular risk, and may furnish the tools to design personalized, epigenetic-based therapies to alleviate the burden of cardiovascular disease in diabetic patients. The present review aims to acquaint the scientific community with the rapidly advancing field of epigenetics and its implications in the cardiovascular complications of diabetes.

https://ift.tt/2OyVeuP

Late growth of infantile hemangiomas in children >3 years of age: A retrospective study

Publication date: Available online 5 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Kathleen F. O'Brien, Sonal D. Shah, Elena Pope, Roderic J. Phillips, Francine Blei, Eulalia Baselga, Maria C. Garzon, Catherine McCuaig, Anita N. Haggstrom, Peter H. Hoeger, James R. Treat, Marissa J. Perman, Jane S. Bellet, Xavier Cubiró, Jeffrey Poole, Ilona J. Frieden

Background

The proliferative phase of infantile hemangiomas (IHs) is usually complete by 9 months of life. Late growth beyond age 3 years is rarely reported.

Objective

To describe the demographic and clinic characteristics of a cohort of patients with late growth of IH, defined as growth in a patient >3 years of age.

Methods

A multicenter, retrospective cohort study.

Results

In total, 59 patients, 85% of which were female, met the inclusion criteria. The mean first episode of late growth was 4.3 (range 3-8.5) years. Head and neck location (55/59; 93%) and presence of deep hemangioma (52/59; 88%) were common characteristics. Posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities (PHACE) syndrome was noted in 20 of 38 (53%) children with segmental facial IH. Systemic therapy (corticosteroid or β-blocker) was given during infancy in 58 of 59 (98%) and 24 of 59 (41%) received systemic therapy (β-blockers) for late IH growth.

Limitations

The retrospective nature and ascertainment by investigator recall are limitations of the study.

Conclusion

Late IH growth can occur in children after 3 years of age. Risk factors include head and neck location, segmental morphology, and involvement of deep dermal/subcutaneous tissues.

https://ift.tt/2pBp0AT

Use of disposable blade for harvesting epidermal skin graft

Publication date: Available online 4 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Rajsmita Bhattacharjee, Keshavamurthy Vinay, Davinder Parsad

https://ift.tt/2IFMP39

Three dimensional evaluation of soft tissue after orthognathic surgery

Abstract

Background

To evaluate the nasolabial soft tissue change three-dimensionally after orthognathic surgery, using a structured light scanner.

Methods

Thirty-two malocclusion patients, who underwent orthognathic surgery, were evaluated. CBCT and 3D facial scans were obtained before surgery and 3 months after surgery. The 3D changes in the 26 landmarks, and the relative ratio of the soft tissue movement to the bony movement, were evaluated.

Results

In the Le Fort I advancement patients, the nasal tip moved 17% forward, compared to the maxillary bony movement, but the nasal prominence decreased 15%. The alar width increased 4 mm after the advancement, and the width decreased 4.7 mm after Le Fort I setback. The relative ratio of the soft tissue movement to the bony movement after bilateral sagittal split osteotomy was about 66% at the Li point in the anteroposterior direction, and it was 21% in the Le Fort I advancement and 14% in Le Fort I setback at the Ls point.

Conclusion

Alar cinch suturing may not be sufficient to overcome the effect of the maxilla advancement compressing the nasal complex. Alar width widening was prevented in Le Fort I setback. However, it is uncertain that the alar cinch suturing was solely responsible. The soft tissue around the mandible tends to accompany the bony movement more than the maxillary area. In addition, structured light scanning system proved to be a useful tool to evaluate the nasolabial soft tissue.

https://ift.tt/2BY6fyT

Bite injuries caused by transcranial electrical stimulation motor-evoked potentials’ monitoring: incidence, associated factors, and clinical course

Abstract

Purpose

The incidence of bite injuries associated with transcranial electrical stimulation motor-evoked potentials monitoring reportedly ranges from 0.13 to 0.19%. However, in clinical practice, bite injuries appear to occur more frequently than previously reported. Our aim was to identify the incidence of and perioperative risk factors associated with bite injuries caused by transcranial electrical stimulation motor-evoked potential monitoring.

Methods

Patients who underwent elective surgery with transcranial electrical stimulation motor-evoked potential monitoring at a single tertiary hospital in Japan between June 2017 and December 2017 were included in this study. All patients were assessed by oral surgeons preoperatively and postoperatively. The associated factors with bite injuries were explored by the univariate analysis.

Results

12 of 186 patients experienced 13 bite injuries, including three lip, six oral mucosa, and four tongue injuries. No patient required suture repair. 11 of 12 patients had uneventful postoperative courses and were cured within 12 postoperative days. One patient with a tongue ulcer and a hematoma had difficulty in oral intake and persistent dysgeusia. Patient severe movement during transcranial electrical stimulation motor-evoked potential monitoring was associated with bite injuries (p = 0.03).

Conclusions

The incidence of bite injuries assessed by oral surgeons was 6.5% in patients with transcranial electrical stimulation motor-evoked potential monitoring, and the patients with severe movement during the monitoring tended to incur bite injuries. In rare cases, transcranial electrical stimulation motor-evoked potential monitoring may cause difficulty in oral intake and dysgeusia.

https://ift.tt/2QwltPU

Thoracic spinal cord injury without radiologic abnormality in a pediatric patient case report

$A-B: A. Sagittal bone window of spine showing normal alignment and no fracture. B. Sagittal T1 contrast enhanced sequence showing a narrowed spinal cord from T7 to T10 that could correspond to gliosis and edema.$

Abstract

Spinal Cord Injury Without Radiologic Abnormality (SCIWORA) accounts for up to 19% of spinal cord related lesions in pediatric population, mostly comprising the cervical spine. A 2-year-old patient is presented, who suffered a motor-vehicle accident. After being admitted, neither X-Ray nor spinal TC scan showed any structural abnormalities. Neurological examination showed complete sensory and motor loss under T7 as well as bladder and bowel dysfunction. Magnetic resonance imaging (MRI) showed spinal cord lesion extending from T7 to T10. The patient was treated with external immobilization and physical therapy. Thoracic SCIWORA is an uncommon diagnosis that should be considered in pediatric patients who suffer spinal trauma. Spinal cord MRI has proven to be the most accurate modality for diagnosis.

https://ift.tt/2y1iKH9

Ectopic jejunal pancreas with pancreatitis mistaken for a post-transplant lymphoproliferative disease in an immunosuppressed kidney transplant patient

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Abstract

An ectopic pancreas, also known as pancreatic rest or heterotopic pancreas, consists of pancreatic tissue found in a location with no continuity with the anatomic pancreas. This lesion can occasionally cause gastrointestinal obstruction, ulceration or become inflamed and cause ectopic pancreatitis. We present the case of a 29-year-old immunocompromised female patient due to a previous kidney transplant. She presented with nausea and vague abdominal discomfort and was admitted for investigation and treatment of an acute kidney injury. A small bowel mass of unknown etiology was incidentally found on abdominal computed tomography imaging. Due to the high suspicion of a post-transplant lymphoproliferative disease, a surgical exploration took place and revealed the presence of a pancreatic rest with chronic pancreatitis. Ectopic pancreas diagnosis is challenging and surgical exploration is warranted when a neoplastic process is suspected.

https://ift.tt/2PcacDT

Adenocarcinoma arising in a colonic interposition after esophagectomy for benign stricture and review of the literature

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Abstract

Colon interposition in oesophageal replacement after oesophagectomy for benign strictures is associated with significant perioperative complications that carry high morbidity and mortality. Long-term sequelae such as further strictures and colonic redundancy are frequent. Adenocarcinoma in the colonic graft is rare. A 70-year-old female presented to our clinic with symptoms of dysphagia. When she was 51 years, she underwent left colonic oesophageal interposition for an oesophageal stricture caused by caustic ingestion. Studies revealed colonic adenocarcinoma in interposed colonic graft, with latero-cervical lymph nodes. She was proposed to neoadjuvant chemotherapy. Although long-term risk analysis is lacking, it's not unreasonable to propose endoscopic screening according to general colonic cancer guidelines in patients with colonic interposition in oesophageal replacement after oesophagectomy.

https://ift.tt/2y2UnZX

A Case series of candy cane limb syndrome after laparoscopic Roux-en-Y gastric bypass

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Abstract

Candy cane syndrome is a rare complication reported in bariatric patients following Roux-en-Y gastric bypass. It occurs when there is an excessive length of roux limb proximal to gastrojejunostomy, creating the possibility for food particles to lodge and remain in the blind redundant limb. Patients present with non-specific symptoms such as abdominal pain associated with nausea and vomiting. Most remain undiagnosed as the disease process is poorly described. We report three cases of candy cane syndrome treated successfully at our institution.

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Aortic valve reconstruction with autologous pericardium in a patient with osteogenesis imperfecta

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Abstract

Cardiac valve surgery for patients with osteogenesis imperfecta is associated with a high incidence of complications such as perioperative bleeding and valve detachment. In this report, we present a patient who was diagnosed with osteogenesis imperfecta and severe aortic insufficiency and also discussed treatment options.

https://ift.tt/2y0WcGO

Renal clear cell carcinoma metastasis to submandibular gland: case report and review of the literature

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Abstract

Metastases from renal clear cell carcinoma (RCCC) to the head and neck (HN) region are rare, representing 8–14% of all RCCC metastases, with the thyroid gland being the most common site of RCCC metastasis in the HN. Metastatic tumors that are located in the salivary glands have a prevalence of 5%, while the submandibular gland is only involved in 1% of the cases. We present the case of a 74-year-old female patient with metastasis to the submandibular gland, 11 years after radical nephrectomy for a RCCC.

https://ift.tt/2P8Jzj7

Ascaris lumbricoides and its almost deadly complication

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Abstract

Parasitic infections are still a burden in developing countries. The lack of sanitation and hygiene measures can result in an increase in morbidity and mortality due to parasitic infections. Surgery may be needed to treat serious complications caused by some of these parasites. Ascaris lumbricoides is one of the most common parasites and although infections are usually mild, severe complications, although rare, still exist. We present a case of a patient from the Ecuadorean Amazon region with limited access to drinking water. She presented to the emergency room with abdominal pain and a mass in the abdomen. After surgery, a mass with a perforation due to Ascaris was discovered. After discharge and due to lack of follow up and self-care, she became infected again, this time making her prognosis more complex and her clinical presentation more difficult. However, after proper clinical and surgical management, patient fully recovered.

https://ift.tt/2y0Dyif

Continuing Medical Education Calendar

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s):

https://ift.tt/2OHPyOY

Information for Readers

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s):

https://ift.tt/2NpT9g1

Editorial Board

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s):

https://ift.tt/2OFZj00

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s):

https://ift.tt/2NoLOxm

Brief Overview of This Month's JACI

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s):

https://ift.tt/2OyPAJ9

Cover 1

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s):

https://ift.tt/2NoLKh6

Correction

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s):

https://ift.tt/2OIPgY6

GM-CSF therapy in human caspase recruitment domain–containing protein 9 deficiency

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s): Rebecca A. Drummond, Fatema Tuz Zahra, Mukil Natarajan, Muthulekha Swamydas, Amy P. Hsu, L. Joseph Wheat, Christina Gavino, Donald C. Vinh, Steven M. Holland, Constantinos M. Mikelis, Michail S. Lionakis

https://ift.tt/2NpTOhv

Nuclear factor (erythroid-derived 2)-like-2 pathway modulates substance P–induced human mast cell activation and degranulation in the hair follicle

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s): Laura Jadkauskaite, Rajia Bahri, Nilofer Farjo, Bessam Farjo, Gail Jenkins, Ranjit Bhogal, Iain Haslam, Silvia Bulfone-Paus, Ralf Paus

https://ift.tt/2OFZdWc

Evolution of IgE responses to multiple allergen components throughout childhood

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s): Rebecca Howard, Danielle Belgrave, Panagiotis Papastamoulis, Angela Simpson, Magnus Rattray, Adnan Custovic

Background

There is a paucity of information about longitudinal patterns of IgE responses to allergenic proteins (components) from multiple sources.

Objectives

This study sought to investigate temporal patterns of component-specific IgE responses from infancy to adolescence, and their relationship with allergic diseases.

Methods

In a population-based birth cohort, we measured IgE to 112 components at 6 follow-ups during childhood. We used a Bayesian method to discover cross-sectional sensitization patterns and their longitudinal trajectories, and we related these patterns to asthma and rhinitis in adolescence.

Results

We identified 1 sensitization cluster at age 1, 3 at age 3, 4 at ages 5 and 8, 5 at age 11, and 6 at age 16 years. "Broad" cluster was the only cluster present at every follow-up, comprising components from multiple sources. "Dust mite" cluster formed at age 3 years and remained unchanged to adolescence. At age 3 years, a single-component "Grass" cluster emerged, which at age 5 years absorbed additional grass components and Fel d 1 to form the "Grass/cat" cluster. Two new clusters formed at age 11 years: "Cat" cluster and "PR-10/profilin" (which divided at age 16 years into "PR-10" and "Profilin"). The strongest contemporaneous associate of asthma at age 16 years was sensitization to dust mite cluster (odds ratio: 2.6; 95% CI: 1.2-6.1; P < .05), but the strongest early life predictor of subsequent asthma was sensitization to grass/cat cluster (odds ratio: 3.5; 95% CI: 1.6-7.4; P < .01).

Conclusions

We describe the architecture of the evolution of IgE responses to multiple allergen components throughout childhood, which may facilitate development of better diagnostic and prognostic biomarkers for allergic diseases.

https://ift.tt/2NpTL5j

PD-1 blocks lytic granule polarization with concomitant impairment of integrin outside-in signaling in the natural killer cell immunological synapse

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s): Yu Huang, Zhiying Chen, Joon Hee Jang, Mirza S. Baig, Grant Bertolet, Casey Schroeder, Shengjian Huang, Qian Hu, Yong Zhao, Dorothy E. Lewis, Lidong Qin, Michael Xi Zhu, Dongfang Liu

Background

The inhibitory receptor programmed cell death protein 1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic viral infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized.

Objective

We sought to determine the effect of PD-1 signaling on NK cells.

Methods

PD-1 was overexpressed in CD16-KHYG-1 (a human NK cell line with both antibody-dependent cellular cytotoxicity through CD16 and natural cytotoxicity through NKG2D) cells and stimulated by exposing the cells to NK-sensitive target cells expressing programmed death ligand 1 (PD-L1).

Results

PD-1 engagement by PD-L1 specifically blocked NK cell–mediated cytotoxicity without interfering with the conjugation between NK cells and target cells. Further examination showed that PD-1 signaling blocked lytic granule polarization in NK cells, which was accompanied by failure of integrin-linked kinase, a key molecule in the integrin outside-in signaling pathway, to accumulate in the immunological synapse after NK–target cell conjugation.

Conclusion

Our results suggest that NK cell cytotoxicity is inhibited by PD-1 engagement, which blocks lytic granule polarization to the NK cell immunological synapse with concomitant impairment of integrin outside-in signaling. This study provides novel mechanistic insights into how PD-1 inhibition disrupts NK cell function.

Graphical abstract

Graphical abstract for this article

https://ift.tt/2OFZatu

ORAI1 mutations abolishing store-operated Ca2+ entry cause anhidrotic ectodermal dysplasia with immunodeficiency

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s): Jayson Lian, Mario Cuk, Sascha Kahlfuss, Lina Kozhaya, Martin Vaeth, Frédéric Rieux-Laucat, Capucine Picard, Melina J. Benson, Antonia Jakovcevic, Karmen Bilic, Iva Martinac, Peter Stathopulos, Imre Kacskovics, Thomas Vraetz, Carsten Speckmann, Stephan Ehl, Thomas Issekutz, Derya Unutmaz, Stefan Feske

Background

Store-operated Ca²⁺ entry (SOCE) through Ca²⁺ release–activated Ca²⁺ channels is an essential signaling pathway in many cell types. Ca²⁺ release–activated Ca²⁺ channels are formed by ORAI1, ORAI2, and ORAI3 proteins and activated by stromal interaction molecule (STIM) 1 and STIM2. Mutations in the ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and nonimmunologic symptoms.

Objective

We performed molecular and immunologic analysis of patients with CID, anhidrosis, and ectodermal dysplasia of unknown etiology.

Methods

We performed DNA sequencing of the ORAI1 gene, modeling of mutations on ORAI1 crystal structure, analysis of ORAI1 mRNA and protein expression, SOCE measurements, immunologic analysis of peripheral blood lymphocyte populations by using flow cytometry, and histologic and ultrastructural analysis of patient tissues.

Results

We identified 3 novel autosomal recessive mutations in ORAI1 in unrelated kindreds with CID, autoimmunity, ectodermal dysplasia with anhidrosis, and muscular dysplasia. The patients were homozygous for p.V181SfsX8, p.L194P, and p.G98R mutations in the ORAI1 gene that suppressed ORAI1 protein expression and SOCE in the patients' lymphocytes and fibroblasts. In addition to impaired T-cell cytokine production, ORAI1 mutations were associated with strongly reduced numbers of invariant natural killer T and regulatory T (Treg) cells and altered composition of γδ T-cell and natural killer cell subsets.

Conclusion

ORAI1 null mutations are associated with reduced numbers of invariant natural killer T and Treg cells that likely contribute to the patients' immunodeficiency and autoimmunity. ORAI1-deficient patients have dental enamel defects and anhidrosis, representing a new form of anhidrotic ectodermal dysplasia with immunodeficiency that is distinct from previously reported patients with anhidrotic ectodermal dysplasia with immunodeficiency caused by mutations in the nuclear factor κB signaling pathway (IKBKG and NFKBIA).

Graphical abstract

Graphical abstract for this article

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Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s): Paul Tuijnenburg, Hana Lango Allen, Siobhan O. Burns, Daniel Greene, Machiel H. Jansen, Emily Staples, Jonathan Stephens, Keren J. Carss, Daniele Biasci, Helen Baxendale, Moira Thomas, Anita Chandra, Sorena Kiani-Alikhan, Hilary J. Longhurst, Suranjith L. Seneviratne, Eric Oksenhendler, Ilenia Simeoni, Godelieve J. de Bree, Anton T.J. Tool, Ester M.M. van Leeuwen

Background

The genetic cause of primary immunodeficiency disease (PID) carries prognostic information.

Objective

We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource–Rare Diseases cohort.

Methods

In the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a novel Bayesian method identified nuclear factor κB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n = 390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by means of analysis of structural protein data. Immunophenotyping, immunoblotting, and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype cosegregation analyses.

Results

Both sporadic and familial cases demonstrated evidence of the noninfective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%), and autoimmune disease (48%), features prior studies correlated with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B-lymphocyte differentiation. Detailed assessment of B-lymphocyte numbers, phenotype, and function identifies the presence of an increased CD21^low B-cell population. Combined with identification of the disease-causing variant, this distinguishes between healthy subjects, asymptomatic carriers, and clinically affected cases.

Conclusion

We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.

Graphical abstract

Graphical abstract for this article

https://ift.tt/2OFZ8So

Autonomous role of Wiskott-Aldrich syndrome platelet deficiency in inducing autoimmunity and inflammation

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s): Lucia Sereni, Maria Carmina Castiello, Francesco Marangoni, Achille Anselmo, Dario di Silvestre, Sara Motta, Elena Draghici, Stefano Mantero, Adrian J. Thrasher, Silvia Giliani, Alessandro Aiuti, Pierluigi Mauri, Luigi D. Notarangelo, Marita Bosticardo, Anna Villa

Background

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by eczema, infections, and susceptibility to autoimmunity and malignancies. Thrombocytopenia is a constant finding, but its pathogenesis remains elusive.

Objective

To dissect the basis of the WAS platelet defect, we used a novel conditional mouse model (CoWas) lacking Wiskott-Aldrich syndrome protein (WASp) only in the megakaryocytic lineage in the presence of a normal immunologic environment, and in parallel we analyzed samples obtained from patients with WAS.

Methods

Phenotypic and functional characterization of megakaryocytes and platelets in mutant CoWas mice and patients with WAS with and without autoantibodies was performed. Platelet antigen expression was examined through a protein expression profile and cluster proteomic interaction network. Platelet immunogenicity was tested by using ELISAs and B-cell and platelet cocultures.

Results

CoWas mice showed increased megakaryocyte numbers and normal thrombopoiesis in vitro, but WASp-deficient platelets had short lifespan and high expression of activation markers. Proteomic analysis identified signatures compatible with defects in cytoskeletal reorganization and metabolism yet surprisingly increased antigen-processing capabilities. In addition, WASp-deficient platelets expressed high levels of surface and soluble CD40 ligand and were capable of inducing B-cell activation in vitro. WASp-deficient platelets were highly immunostimulatory in mice and triggered the generation of antibodies specific for WASp-deficient platelets, even in the context of a normal immune system. Patients with WAS also showed platelet hyperactivation and increased plasma soluble CD40 ligand levels correlating with the presence of autoantibodies.

Conclusion

Overall, these findings suggest that intrinsic defects in WASp-deficient platelets decrease their lifespan and dysregulate immune responses, corroborating the role of platelets as modulators of inflammation and immunity.

Graphical abstract

Graphical abstract for this article

https://ift.tt/2NpdfXU

CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s): Hung-Wei Cheng, Lucas Onder, Jovana Cupovic, Maximilian Boesch, Mario Novkovic, Natalia Pikor, Ignazio Tarantino, Regulo Rodriguez, Tino Schneider, Wolfram Jochum, Martin Brutsche, Burkhard Ludewig

Background

A particular characteristic of non–small cell lung cancer is the composition of the tumor microenvironment with a very high proportion of fibroblastic stromal cells (FSCs).

Objective

Lapses in our basic knowledge of fibroblast phenotype and function in the tumor microenvironment make it difficult to define whether FSC subsets exist that exhibit either tumor-promoting or tumor-suppressive properties.

Methods

We used gene expression profiling of lung versus tumor FSCs from patients with non–small cell lung cancer. Moreover, CCL19-expressing FSCs were studied in transgenic mouse models by using a lung cancer metastasis model.

Results

CCL19 mRNA expression in human tumor FSCs correlates with immune cell infiltration and intratumoral accumulation of CD8⁺ T cells. Mechanistic dissection in murine lung carcinoma models revealed that CCL19-expressing FSCs form perivascular niches to promote accumulation of CD8⁺ T cells in the tumor. Targeted ablation of CCL19-expressing tumor FSCs reduced immune cell recruitment and resulted in unleashed tumor growth.

Conclusion

These data suggest that a distinct population of CCL19-producing FSCs fosters the development of an immune-stimulating intratumoral niche for immune cells to control cancer growth.

Graphical abstract

Graphical abstract for this article

https://ift.tt/2OIQd2Y

A Jagged 1–Notch 4 molecular switch mediates airway inflammation induced by ultrafine particles

Publication date: October 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 4

Author(s): Mingcan Xia, Hani Harb, Arian Saffari, Constantinos Sioutas, Talal A. Chatila

Background

Exposure to traffic-related particulate matter promotes asthma and allergic diseases. However, the precise cellular and molecular mechanisms by which particulate matter exposure acts to mediate these effects remain unclear.

Objective

We sought to elucidate the cellular targets and signaling pathways critical for augmentation of allergic airway inflammation induced by ambient ultrafine particles (UFP).

Methods

We used in vitro cell-culture assays with lung-derived antigen-presenting cells and allergen-specific T cells and in vivo mouse models of allergic airway inflammation with myeloid lineage-specific gene deletions, cellular reconstitution approaches, and antibody inhibition studies.

Results

We identified lung alveolar macrophages (AM) as the key cellular target of UFP in promoting airway inflammation. Aryl hydrocarbon receptor–dependent induction of Jagged 1 (Jag1) expression in AM was necessary and sufficient for augmentation of allergic airway inflammation by UFP. UFP promoted T_H2 and T_H17 cell differentiation of allergen-specific T cells in a Jag1- and Notch 4–dependent manner. Treatment of mice with an anti–Notch 4 antibody abrogated exacerbation of allergic airway inflammation induced by UFP.

Conclusion

UFP exacerbate allergic airway inflammation by promoting a Jag1-Notch 4–dependent interaction between AM and allergen-specific T cells, leading to augmented T_H cell differentiation.

Graphical abstract

Graphical abstract for this article

https://ift.tt/2NniRlf

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Παρασκευή 5 Οκτωβρίου 2018

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