Editorial Board

Publication date: June 2018
Source:Operative Techniques in Otolaryngology-Head and Neck Surgery, Volume 29, Issue 2





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Miltefosine has post-antifungal effect and induces apoptosis in Cryptococcus yeasts [PublishAheadOfPrint]

Cryptococcus spp. are common opportunistic fungal pathogens, particularly in HIV patients. The approved drug miltefosine (MFS) has potential as an alternative antifungal against cryptococcosis; however, the mechanism of action of MFS in Cryptococcus is poorly understood. Here, we examined the effects of MFS on C. neoformans and C. gattii yeasts (planktonic and biofilm lifestyles), to clarify its mechanism of action. MFS presented inhibitory and fungicidal effects against planktonic Cryptococcus cells, with similar activity against dispersion biofilm cells, while sessile biofilm cells were less sensitive to MFS. Interestingly, MFS had post-antifungal effect on Cryptococcus, with a proliferation delay of up to 8.15 h after short exposure to fungicidal doses. MFS at fungicidal concentrations increased plasma membrane permeability, likely due to direct interaction with ergosterol, as suggested by competition assays with exogenous ergosterol. Moreover, MFS reduced the mitochondrial membrane potential, increased ROS production, and induced DNA fragmentation and condensation, all of which are hallmarks of apoptosis. Transmission electron microscopy analysis showed that MFS-treated yeasts had a reduced mucopolysaccharide capsule (confirmed by morphometry in light microscopy), plasma membrane irregularities, mitochondrial swelling and a less conspicuous cell wall. Our results suggest that MFS increases plasma membrane permeability in Cryptococcus via interaction with ergosterol, and also affects the mitochondrial membrane, eventually leading to apoptosis, in line with its fungicidal activity. These findings confirm the potential of MFS as an antifungal against C. neoformans and C. gattii, and warrants further studies to establish clinical protocols for MFS use against cryptococcosis.

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Anti-trypanosomal 8-hydroxyl naphthyridines are chelators of divalent transition metals [PublishAheadOfPrint]

Lack of information regarding the mechanisms of action (MoA) or specific molecular targets of phenotypically active compounds can prove a barrier to their development as chemotherapeutic agents. Here, we report the results of our orthogonal genetic, molecular and biochemical studies to determine the MoA of a novel 7-substituted 8-hydroxy-1,6-naphthyridine (8-HNT) series that display promising activity against Trypanosoma brucei and Leishmania donovani. High-throughput loss-of-function genetic screens in T. brucei highlighted two probable zinc transporters associated with resistance to these compounds. These transporters localized to the parasite Golgi. Directed by these findings, the role of zinc and other divalent cations in the MoA of these compounds was investigated. 8-HNT compounds were found to directly deplete intracellular levels of Zn²⁺ while the addition of exogenous Zn²⁺ and Fe²⁺ reduced the potency of compounds from this series. Detailed biochemical analyses confirmed that 8-HNT compounds bind directly to a number of divalent cations, predominantly Zn²⁺, Fe²⁺ and Cu²⁺, forming 2:1 complexes with one of these cations. Collectively, our studies demonstrate transition metal depletion, due to chelation, as the MoA of the 8-HNT series of compounds. Strategies to improve the selectivity of 8-HNT compounds are discussed.

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Fragments of the non-lytic proline-rich antimicrobial peptide Bac5 kill E. coli cells by inhibiting protein synthesis. [PublishAheadOfPrint]

Unlike most antimicrobial peptides (AMPs), the main mode of action of the subclass of proline-rich antimicrobial peptides (PrAMPs) is not based on disruption of the bacterial membrane. Instead, PrAMPs exploit the inner membrane transporters SbmA and YjiL/MdtM to pass through the bacterial membrane and enter the cytosol of specific Gram-negative bacteria, where they exert an inhibitory effect on protein synthesis. Despite sharing a high proline and arginine content with other characterized PrAMPs, the PrAMP Bac5 has a low sequence identity with them. Here we investigated the mode of action of three N-terminal Bac5 fragments, Bac5 (1-15), Bac5 (1-25) and Bac5 (1-31). We could show that Bac5 (1-25) and Bac5 (1-31) retain excellent antimicrobial activity towards Escherichia coli and low toxicity towards eukaryotic cells, whereas Bac5 (1-15) was inactive. Bac5 (1-25) and Bac5 (1-31) inhibited bacterial protein synthesis in vitro and in vivo. Competition assays suggest that the binding site of Bac5 is within the ribosomal tunnel, where it prevents the transition from the initiation to the elongation phase of translation, as reported for other PrAMPs, such as the bovine PrAMP Bac7. Surprisingly, unlike Bac7, Bac5 (1-25) exhibited species-specific inhibition, being an excellent inhibitor of protein synthesis on E. coli ribosomes but a poor inhibitor on Thermus thermophilus ribosomes. This indicates that while Bac5 most likely has an overlapping binding site with Bac7, the mode of interaction is distinct, suggesting that Bac5 fragments may be interesting alternative lead compounds for the development of new antimicrobial agents.

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Antibacterial spectrum of a tetrazole-based reversible inhibitor of serine {beta}-lactamases [PublishAheadOfPrint]

CTX-M is the most prevalent family of extended-spectrum β-lactamases. We recently developed a tetrazole-derived non-covalent inhibitor of CTX-M-9. Here, we present biochemical and microbiological activity of this inhibitor across a representative panel of serine β-lactamases and Gram-negative bacteria. The compound displayed significant activity against all major subgroups of CTX-M, including CTX-M-15, while exhibiting some low-level inhibition of other serine β-lactamases. Complex crystal structures with CTX-M-14 S237A mutant and CTX-M-27 illustrate the binding contribution of specific active site residues on the β3 strand. In vitro pharmacokinetic studies revealed drug-like properties and positive prospects for further optimization. These studies suggest that tetrazole-based compounds can provide novel chemotypes for future serine β-lactamase inhibitor discovery.

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Antimicrobial Efficacy and Safety of a Novel Gas Plasma-Activated Catheter Lock Solution [PublishAheadOfPrint]

Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans in mature biofilms were reduced by 6 – 8 orders of magnitude with a PAD lock for 60 minutes. Subsequent 24-hour incubation of PAD-treated samples resulted in no detectable regrowth of viable bacteria or fungi. As a comparison, the use of a minocycline/EDTA/ethanol lock solution for 60 minutes led to regrowth of bacteria and fungi, up to 10⁷ – 10⁹ CFU/ml, in 24 hours. The PAD lock solution had minimal impact on human umbilical vein endothelial cell viability, whereas the minocycline/EDTA/ethanol solution elicited cell death in nearly half of human endothelial cells. Additionally, PAD treatment caused little topological change to catheter materials. In conclusion, PAD represents a novel antibiotic-free, non-cytotoxic lock solution that elicits rapid and broad-spectrum eradication of biofilm-laden microbes and which shows promise for the prevention and treatment of intravascular catheter infections.

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Recommendations to address the difficulties encountered when determining linezolid resistance from whole genome sequencing data [PublishAheadOfPrint]

Mutations associated with linezolid resistance within the V domain of 23S rRNA are annotated using an Escherichia coli numbering system. The 23S rRNA gene varies in length, nucleotide sequence and copy number between bacterial species. Consequently, this numbering system is not intuitive and can lead to confusion when locating mutation sites using whole genome sequencing data. Using the mutation G2576T as an example, we demonstrate the difficulties associated with using the E. coli numbering system.

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Chromosomally Encoded mcr-5 in Colistin non-susceptible Pseudomonas aeruginosa [PublishAheadOfPrint]

Whole genome sequencing (WGS) of historical Pseudomonas aeruginosa clinical isolates identified a chromosomal copy of mcr-5 within a Tn3-like transposon in P. aeruginosa MRSN 12280. The isolate was non-susceptible to colistin by broth microdilution and genome analysis revealed no mutations known to confer colistin resistance. To the best of our knowledge, this is the first report of mcr in colistin non-susceptible P. aeruginosa.

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Lipopeptide Paenipeptin Analogues Potentiate Clarithromycin and Rifampicin against Carbapenem-Resistant Pathogens [PublishAheadOfPrint]

Two paenipeptin analogues at 4 μg/ml potentiated clarithromycin and rifampicin against carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae strains. The combined treatment significantly increased their antibacterial efficacy in a microbiological medium and in human serum in vitro at therapeutically-relevant concentrations. Moreover, these two paenipeptins analogues showed low cytotoxicity against a human kidney cell line. Therefore, the combination therapy with paenipeptins may be an option for the treatment of antibiotic-resistant bacterial infections.

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Disruption of mpl Activates {beta}-Lactamase Production in Stenotrophomonas maltophilia and Pseudomonas aeruginosa Clinical Isolates. [PublishAheadOfPrint]

The hyperproduction of chromosomally encoded β-lactamases is a key method of acquired resistance to ceftazidime, aztreonam, and when seen in backgrounds having reduced envelope permeability, carbapenems. Here we show that loss of Mpl, a UDP-muramic acid/peptide ligase, is a common and previously overlooked cause of chromosomally encoded β-lactamase hyperproduction in clinical isolates of Stenotrophomonas maltophilia and Pseudomonas aeruginosa, important pathogens notorious for their β-lactam resistant phenotypes.

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Clofazimine for the treatment of Mycobacterium kansasii [PublishAheadOfPrint]

Mycobacterium kansasii pulmonary infection is global problem. Standard combination therapy consists of isoniazid 300 mg/day, rifampin 600 mg/day, and ethambutol 15 mg/kg/day for 18 months. Co-incubation of M. kansasii with different clofazimine concentrations over 7 days in test-tubes resulted in maximal kill (E_max) of 2.03 log₁₀ CFU/mL below day 0. The concentration associated with E_max was 110 times the minimum inhibitory concentration. Next, the effect of human-like concentration-time profiles of clofazimine human-equivalent doses ranging between 0 to 200 mg daily for 21 days were examined in the intracellular-infection hollow fiber model of M. kansasii (HFS-Mkn). On day 14, when clofazimine microbial effect was maximal, the E_max was 2.57 log₁₀ CFU/mL while dose associated with E_max was 100 mg/day. However, no dose killed M. kansasii to below day 0. Thus, the antimicrobial effect of clofazimine monotherapy in the HFS-Mkn was modest. Human equivalent concentration-time profiles of standard combination therapy and doses were used as comparator in the HFS-Mkn. On day 14, standard therapy had killed 2.32 log₁₀ CFU/mL below day 0. The effect of standard therapy was consistent with a bi-exponential decline with kill rate constants of 1.85 per day (half-life=0.37 days) and 0.06 per day (half-life=12.76 days), r²>0.99. This means that standard therapy would take 9.3-12 months to completely eliminate M. kansasii in the model, which is consistent with clinical observations. This observation for standard therapy means that the modest to poor effect of clofazimine on M. kansasii identified here is likely to be the same in the clinic.

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Comparison of in vitro activity and MIC distributions between the novel oxazolidinone delpazolid and linezolid against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis in China [PublishAheadOfPrint]

Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis (MTB). In this study, we compared in vitro activity and minimal inhibitory concentration (MIC) distributions between delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant (MDR) and extensively drug-resistant MTB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC and rplD genes were analyzed to reveal potential mechanism(s) underlying observed oxazolidinone resistance. A total of 240 MTB isolates were enrolled in this study, including 120 MDR-TB and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC₉₀ values for MTB isolates were 0.25 mg/L and 0.5 mg/L, respectively. Based upon visual inspection, we tentatively set epidemiological cutoff values (ECOFFs) for MIC determinations at 1.0 mg/L and 2.0 mg/L for linezolid and delpazolid, respectively. Although no significant difference in resistance rate was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly higher proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, one isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC > 16 mg/L) compared to a delpazolid MIC = 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity is comparable to that of linezolid. A novel mutation within rplD was identified that endowed MTB with linezolid, but not delpazolid, resistance.

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Nephrotoxicity Associated with Intravenous Polymyxin B Once versus Twice Daily Dosing Regimen [PublishAheadOfPrint]

Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggests that once daily dosing may reduce the rate and delay the onset of acute kidney injury (AKI).

In a multicenter, retrospective study, we evaluated adult patients with a creatinine clearance (CrCl) ≥30 mL/min who received ≥48h of PMB therapy. The primary endpoint was the difference in rate of AKI comparing once and twice daily PMB dosing. Secondary endpoints included time to AKI and recovery of renal function.

Of 273 eligible patients, 100 from each group were matched based on propensity scores. In the matched groups, nephrotoxicity, defined according to RIFLE criteria, was more frequent with once versus twice daily dosing (47% vs. 17% P=0.0005). After adjusting for residual differences by multivariate conditional logistic regression, once daily dosing was more likely to result in nephrotoxicity (adjusted odds ratio 2.5, 95% CI 1.413-4.541, P=0.002). Among 64 patients who developed AKI, the median onset was similar between groups (7 days with once vs. 6 days with twice daily dosing, P=0.095). Of 37 patients who had their serum creatinine evaluated subsequently, 29/37 (78%) had recovery of renal function. No patient required renal replacement therapy.

Our findings suggest that AKI is significantly more common with PMB once daily as compared to twice daily dosing with no difference in time to AKI. Prospective randomized study is warranted to validate these results.

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Analysis of the tunicamycin biosynthetic gene cluster of Streptomyces chartreusis reveals new insights into tunicamycin production and immunity [PublishAheadOfPrint]

The tunicamycin biosynthetic gene cluster of Streptomyces chartreusis consists of 14 genes (tunA-N) with a high degree of apparent translational coupling. Transcriptional analysis revealed that all of these genes are likely to be transcribed as a single operon from two promoters, tunp1 and tunp2. In frame deletion analysis revealed that just six of these genes (tunABCDEH) are essential for tunicamycin production in the heterologous host Streptomyces coelicolor, while five (tunFGKLN) with likely counterparts in primary metabolism are not necessary, but presumably ensure efficient production of the antibiotic at the onset of tunicamycin biosynthesis. Three genes are implicated in immunity; tunIJ, which encode a two component ABC transporter presumably required for export of the antibiotic, and tunM, which encodes a putative SAM-dependent methyltransferase. Expression of tunIJ or tunM in S. coelicolor conferred resistance to exogenous tunicamycin. The results presented here provide new insights into tunicamycin biosynthesis and immunity.

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Iron restriction to clinical isolates of Candida albicans by the novel chelator DIBI inhibits growth and increases sensitivity to azoles in vitro and in vivo in a murine model of experimental vaginitis [PublishAheadOfPrint]

Candida albicans is an important opportunistic pathogen causing various human infections that are often treated with azole antifungals. The US CDC now regards developing candidal antifungal resistance as a threat, creating a need for new and more effective antifungal treatments. Iron is an essential nutrient for all living cells and there is growing evidence that interference with iron homeostasis of C. albicans can improve its response to antifungals. This study was aimed at establishing whether withholding iron by currently used medical iron chelators and the novel chelator DIBI could restrict growth and also enhance the activity of azoles against clinical isolates of C. albicans. DIBI but not deferoxamine or deferiprone, inhibited growth of C. albicans at relatively low concentrations in vitro and this inhibition was reversed by iron addition. DIBI in combination with various azoles demonstrated stronger growth inhibition than the azoles alone and greatly prolonged inhibition of cell multiplication. In addition, administration of DIBI along with fluconazole (FLC) to mice inoculated with a FLC-sensitive isolate in a model of experimental C. albicans vaginitis showed markedly improved clearance of infection. These results suggest that iron chelation by DIBI has the potential to enhance azole efficacy for the treatment of candidiasis.

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A breath sound analysis in children with cough variant asthma

Publication date: Available online 29 May 2018
Source:Allergology International
Author(s): Mayumi Enseki, Mariko Nukaga, Hiromi Tadaki, Hideyuki Tabata, Kota Hirai, Masahiko Kato, Hiroyuki Mochizuki
BackgroundCough variant asthma (CVA) is characterized by a chronic cough and bronchial hyperresponsiveness without confirmation of wheezing. Using a breath sound analyzer, we evaluate the characteristics of breath sound in children with CVA.MethodsNine children with CVA (median age, 7.0 years) participated. The existence of breath sounds was confirmed by sound spectrogram. Breath sound parameters, the frequency limiting 50% and 99% of the power spectrum (F50 and F99), the roll-off from 600 to 1200 Hz (Slope) and spectrum curve indices, the ratio of the third and fourth area to the total area of the power spectrum (P3/PT and P4/PT) and the ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF75 and RPF50) were calculated before and after β2 agonist inhalation. A spirogram and/or forced oscillation technique were performed in all subjects.ResultsOn a sound spectrogram, wheezing was confirmed in seven of nine patients. All wheezing on the image was polyphonic, and they almost disappeared after β2 agonist inhalation. An analysis of the breath sound spectrum showed that PT, P3/PT, P4/PT, RPF50 and RPF75 were significantly increased after β2 agonist inhalation.ConclusionsChildren with CVA showed a high rate of inaudible wheezing that disappeared after β2 agonist inhalation. Changes in the spectrum curve indices also indicated the bronchial reversibility. These results may suggest the characteristics of CVA in children.



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Biochemical analysis and identification of linear B-cell epitopes from recombinant Sm21.7 antigen from Schistosoma mansoni

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Cíntia M.F. Rezende, Juliana B. Coitinho, Mariana Costa, Marina Rodrigues Silva, Mário Giusta, Roberta Oliveira-Prado, Rodrigo Corrêa-Oliveira, Ronaldo Nagem, Alfredo M. Goes
Schistosoma mansoni tegument is a dynamic host-interactive layer that is an essential source of parasite antigens and a relevant field for schistosome vaccine research. Sm21.7 is a cytoskeleton antigen found in S. mansoni tegument that engenders protection in experimental challenge infection. Because of its crucial role in the parasite tegument and its promising protective capability, Sm21.7 is an exciting target for the development of therapeutic strategies. The present study describes Sm21.7 structural and biophysical features using circular dichroism spectroscopy and identifies linear B-cell epitopes of Sm21.7 using in-silico methods and immunoassay. The Sm21.7 gene was cloned into the pETDEST42 vector, and the recombinant protein was overexpressed in Escherichia coli DE3. The soluble protein was purified by affinity chromatography followed by ion-exchange chromatography. Purified recombinant Sm21.7 was analyzed by circular dichroism spectroscopy which demonstrated that the rSm21.7 structure was comprised of approximately 38% α-helices and its conformation remains stable at temperatures of up to 60 °C. Prediction of rSm21.7 B-cell epitopes was based on amino acid physicochemical properties. Sixteen peptides corresponding to predicted epitopes were synthesized and immunoreactivity assessed by spot peptide array using pooled rSm21.7-immunized mice sera or patients' sera with different clinical forms of S. mansoni infection. Immunoassays revealed that sera from rSm21.7-immunized mice reacted predominantly with peptides located in the dynein-light chain domain (DLC) at the C-terminal region of rSm21.7. Comparative analysis of the antibody response of acute, intestinal and hepatosplenic patients' sera to the Sm21.7 peptides showed that a differential recognition pattern of Sm21.7-derived peptides by intestinal patients' sera might contribute to down-regulate the immune response in chronic intestinal patients. Together, the results may help the development of S. mansoni vaccine strategies based on the rSm21.7 antigen.



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Where Does Health Communication Technology Fit Into Allergy Practice?,

Publication date: Available online 29 May 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Bruce G. Bender




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When symptoms don’t fit: a case series of conversion disorder in the pediatric otolaryngology practice

Conversion disorder refers to functional bodily impairments that can be precipitated by high stress situations including trauma and surgery. Symptoms of conversion disorder may mimic or complicate otolaryngolo...

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The impact of chronic airway disease on symptom severity and global suffering in Canadian rhinosinusitis patients

Patients with Chronic Rhinosinusitis (CRS) can suffer from a significant decline in their quality of life. CRS patients have a high prevalence of comorbid conditions and it is important to understand the impac...

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Ablative fractional laser-assisted photodynamic therapy provides superior long-term efficacy compared to standard methyl aminolevulinate photodynamic therapy for lower extremity Bowen’s disease

Ablative fractional laser-assisted methyl aminolevulinate photodynamic therapy (AFL-MAL-PDT) has shown significantly higher efficacy and lower recurrence rates at 12 months than conventional methyl aminolevulinate photodynamic therapy (MAL-PDT) for the treatment of Bowen's disease (BD). However, long-term follow-up data are not available.

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Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: a retrospective case-control study

Cutaneous adverse events are common with Programmed Death (PD)-1/ PD-Ligand (L)1 inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized.

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A Step Toward Demystifying Melanomas of Unknown Primary Sites

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Management of primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma: A retrospective study

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The feasibility of an allergy management support system (AMSS) for IgE-mediated allergy in primary care

The allergy management support system (AMSS) was developed to assist general practitioners (GPs) to handle the increasing burden of allergic diseases and facilitates the diagnosis and management of allergy. Th...

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Minimal Invasive Endoscopic Ear Surgery: A Two Handed Technique

Abstract

To evaluate the surgical outcome of two handed technique of endoscopic ear surgery with endoscope holder. Retrospective Non Randomized Clinical Study. A total of 547 endoscope holder (Justtach) assisted ear surgeries (331 cartilage tympanoplasties and 216 cholesteatoma surgeries) were operated with Justtach from July 2013 to April 2016 with a follow up period ranging from 12 to 45 months to evaluate its feasibility and results with the technique. The design of the endoscope holder, Justtach is described along with its functioning and maneuvering techniques. In the endoscopic tympanoplasty group, at 1 year follow up, the graft uptake was seen in 323 ears with three residual perforation and 5 recurrent perforations giving a success rate of 97.58%. At the 2 years follow up, the graft uptake was in 322 ears with 6 recurrent perforations and 3 residual perforations with a success rate of 97.28%. Whereas in case of endoscopic cholesteatoma surgery, there was residual cholesteatoma in 5 and recurrent in 6 out of 216 cases. The study reports the successful application and use of endoscope holder in two handed technique of endoscopic ear surgery.

Level of Evidence Level 4.

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Aural Atresia with Cholesteotoma and Its Management Strategies

Abstract

The term congenital aural atresia is used to describe failure of external auditory canal to open. Thus it results in conductive hearing loss. There are ways to improve the transmission of sound to the healthy inner ear, we have performed surgery to open the ear canal and restore the natural sound-conducting mechanism to the inner ear. Thus avoiding multiple surgeries. The study was conducted among patients aged between 12 and 24 years, our study included 8 patients with aural atresia with cholesteotoma. After a detailed examination of patients were subjected to surgery. In our study with the sample size of eight patients Where, all our patients underwent canal wall down mastoidectomy with simultaneous single stage reconstruction of ossicular chain. All our patients were discharge free and Had subjective improvement in hearing with the post operative period was well accomplished to < 35 dB. In our study all eight patients who underwent canal wall down mastoidectomy had good hearing outcome. As to avoid unnecessary recurrence and complications which are usually seen in intact canal wall down mastoidectomies, we suggest canal wall down and single stage reconstruction.

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Evaluation of a Dermoplasty Technique for the Control on Nasal Polyps

Abstract

To evaluate the efficacy of a dermoplasty technique in controlling nasal polyps comparing to the conventional endoscopic approach. Prospective observational study Tertiary private hospital. Twenty-nine patients underwent surgery for replacement of the middle meatus mucosa with skin. Some patients (41.4%) suffered from allergies, 44.8% from asthma, and 27.6% from aspirin intolerance. Polyps were staged according to the Lildholdt system, and patients completed a sino-nasal outcome test (SNOT-22) pre and post-operatively. Also, patients were interrogated as for medication relevant to the nose received pre and post-operatively. In twenty-six patients dermoplasty was applied in one nostril while the contralateral was treated with the conventional endoscopic technique allowing us to compare the two techniques in the same patient. Median follow-up period was 1.2 years (IQR 0.8, 2.0; range 0.4–5.8). Median drop in SNOT-22 score was 38.2 percentage units. Patients (79.3%) controlled symptoms by topical corticosteroids for 2.5–3 months per year at most. Seventy percent (70.8%) reported improvement in subjective olfaction. Results compare favorably to those reported in the literature after functional endoscopic approach. Lildholdt stage dropped post-operatively on both sides but significantly more (p value < 0.001) on the dermoplasty side comparing to the conventional endoscopic side. Dermoplasty appears to outbalance the conventional endoscopic removal of polyps and clearance of paranasal sinuses. No matter how extensive the removal of endonasal tissue, it is not sufficient for controlling nasal polyps unless mucosa is prevented from recovering the denuded areas by the use of a skin graft.

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Management of Unstable Middle Turbinate in Endoscopic Sinus Surgery

Abstract

To propose a simple technique for preservation, medialization and stabilization of the middle turbinate through a planned medial synechiae formation using suction electrocautery between middle turbinate and nasal septum. Study design is Case series. 150 cases of chronic rhino sinusitis who underwent ESS were selected and stabilization of the middle turbinate through a planned medial synechiae formation using suction electrocautery was done as last step and results studied. Adequate medialization was achieved in 141 cases with 94% success rate. This technique of medialization of middle turbinate through a planned medial synechiae formation using cautery between middle turbinate and nasal septum is simple, quick to perform, do not require any special or costly instrument, do not require any special training and thus can be easily done by beginners also and most importantly with good success rate and surgery outcome.

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Temporary Increased Dose of Inhaled Corticosteroids in Yellow Zone, Does It Work?

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.


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Surgical plate fixation of multiple rib fractures: a case report

The healthcare system in developing countries is limited; particularly, medical specialties such as emergency and trauma medicine are underdeveloped. Consequently, trauma injuries sustained in traffic accident...

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AI Beats Dermatologists on Skin Lesion Images

Artificial intelligence (AI) has again been shown to outperform specialists in the diagnostic arena, this time in the detection of both benign and malignant skin lesions.
Medscape Medical News

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Estrogen receptor {beta} controls proliferation of enteric glia and differentiation of neurons in the myenteric plexus after damage [Neuroscience]

Injury to the enteric nervous system (ENS) can cause several gastrointestinal (GI) disorders including achalasia, irritable bowel syndrome, and gastroparesis. Recently, a subpopulation of enteric glial cells with neuronal stem/progenitor properties (ENSCs) has been identified in the adult ENS. ENSCs have the ability of reconstituting the enteric neuronal pool after...

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Heterometallic Ru-Pt metallacycle for two-photon photodynamic therapy [Chemistry]

As an effective and noninvasive treatment of various diseases, photodynamic therapy (PTD) relies on the combination of light, a photosensitizer, and oxygen to generate cytotoxic reactive oxygen species that can damage malignant tissue. Much attention has been paid to covalent modifications of the photosensitizers to improve their photophysical properties and...

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Water dynamics in concentrated electrolytes: Local ion effect on hydrogen-bond jumps rather than collective coupling to ion clusters [Physical Sciences]

Zhang et al. (1) suggest that water rotational dynamics slows down in all concentrated ionic solutions mostly because of a collective effect due to the coupling between water dynamics and the motion of large ion clusters. These conclusions were based on simulations of aqueous NaSCN and KSCN salts, with a...

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Temperature regulates NF-{kappa}B dynamics and function through timing of A20 transcription [Systems Biology]

NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor...

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Reply to Stirnemann et al.: Frame retardation is the key reason behind the general slowdown of water reorientation dynamics in concentrated electrolytes [Physical Sciences]

Stirnemann et al. (1) argue that the general deceleration of water reorientation dynamics in the concentrated electrolytes is not entirely due to the frame retardation, since suppressing frame reorientation entirely leads to a maximum slowdown of 1τreorjump+1τreorframe1τreorjump≈1.6, smaller than the deceleration in many concentrated electrolytes. This same argument, however, can...

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Lead pollution recorded in Greenland ice indicates European emissions tracked plagues, wars, and imperial expansion during antiquity [Environmental Sciences]

Lead pollution in Arctic ice reflects midlatitude emissions from ancient lead–silver mining and smelting. The few reported measurements have been extrapolated to infer the performance of ancient economies, including comparisons of economic productivity and growth during the Roman Republican and Imperial periods. These studies were based on sparse sampling and...

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Little evidence for the vocal similarity hypothesis [Biological Sciences]

Bowling et al. (1) report musical consonance judgements of various musical chords and a model designed to assess their "vocal similarity," claiming the fit between model and data provides evidence that the perceived consonance of tone combinations is explained in part by their "relative similarity to voiced speech sounds." I...

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Correction for Vaidyanathan, Core Concept: Microgrids offer flexible energy generation, for a price [Correction]

CORE CONCEPTS Correction for "Core Concept: Microgrids offer flexible energy generation, for a price," by Gayathri Vaidyanathan, which was first published April 24, 2018; 10.1073/pnas.1804507115 (Proc Natl Acad Sci USA 115:4298–4300). The editors note that on page 4298, right column, last paragraph, line 6, "995 kilowatts" should have appeared as...

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Reply to Goffinet: In consonance, old ideas die hard [Biological Sciences]

Goffinet's complaints (1) about our vocal similarity hypothesis (2) are unwarranted on both practical and theoretical grounds. First, the issue of tuning is a red herring. We used standard just intonation intervals to evaluate the consonance of chords because their role in music across historical and cultural boundaries is foundational...

https://ift.tt/2IXEw6b

Elastic coupling power stroke mechanism of the F1-ATPase molecular motor [Biochemistry]

The angular velocity profile of the 120° F1-ATPase power stroke was resolved as a function of temperature from 16.3 to 44.6 °C using a ΔμATP = −31.25 kBT at a time resolution of 10 μs. Angular velocities during the first 60° of the power stroke (phase 1) varied inversely with...

https://ift.tt/2slKx1B

Retrospective of Charles Pence Slichter (NAS 1967) [Retrospectives]

Charles Pence Slichter died on February 19 of this year at the age of 94. Charlie, as he was known to his friends, was one of the giants of postwar physics, a pioneer of electron and nuclear magnetic resonance (NMR), and a renowned expert on superconductivity, a remarkably influential educator,...

https://ift.tt/2IXEond

The glycolipid GM1 reshapes asymmetric biomembranes and giant vesicles by curvature generation [Chemistry]

The ganglioside GM1 is present in neuronal membranes at elevated concentrations with an asymmetric spatial distribution. It is known to generate curvature and can be expected to strongly influence the neuron morphology. To elucidate these effects, we prepared giant vesicles with GM1 predominantly present in one leaflet of the membrane,...

https://ift.tt/2JeWgcI

The promise of genes for understanding cause and effect [Social Sciences]

The Search for Identification Since the 1980s, social scientists have become increasingly interested in how to make credible claims about cause and effect using observational data (1). Ignited by seminal papers demonstrating the promise of natural experiments (2), the causal revolution has put social scientists on the lookout for "as-if"...

https://ift.tt/2H1miec

Spatial mutation patterns as markers of early colorectal tumor cell mobility [Medical Sciences]

A growing body of evidence suggests that a subset of human cancers grows as single clonal expansions. In such a nearly neutral evolution scenario, it is possible to infer the early ancestral tree of a full-grown tumor. We hypothesized that early tree reconstruction can provide insights into the mobility phenotypes...

https://ift.tt/2kyIHqn

Root-exuded coumarin shapes the root microbiome [Plant Biology]

Roots of land plants grow through soil, one of the most microbially rich and diverse environments on earth (1). A long history of work has revealed that plant roots interact with these microbes and help establish microbial communities distinct from the surrounding soil (2). This is partly because roots provide...

https://ift.tt/2GZwzI3

Calcium, conformational selection, and redox-active tyrosine YZ in the photosynthetic oxygen-evolving cluster [Plant Biology]

In Photosystem II (PSII), YZ (Tyr161D1) participates in radical transfer between the chlorophyll donor and the Mn4CaO5 cluster. Under flashing illumination, the metal cluster cycles among five Sn states, and oxygen is evolved from water. The essential YZ is transiently oxidized and reduced on each flash in a proton-coupled electron...

https://ift.tt/2ISU6jw

Biological electron transport goes the extra mile [Microbiology]

Microorganisms stand out by the creative ways in which they gain energy during respiration. Using versatile metabolic networks, respiratory microorganisms harvest electrons from organic or inorganic donor molecules and transfer them to specialized electron transport chains, which redirect their flow toward a terminal electron acceptor. Respiratory electrons move with a...

https://ift.tt/2sn95Y5

In This Issue [This Week in PNAS]

Lead pollution in Greenland ice links emissions and economic activity Ice-core analysis. Lead and silver ore mining powered ancient economies, but previously reported measurements of lead pollution in Arctic ice were based on sparse sampling and inconclusive dating. Joseph McConnell et al. (pp. 5726–5731) used precisely dated measurements of lead...

https://ift.tt/2IVQM78

Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing [Engineering]

Orthopedic implant infections are a significant clinical problem, with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with high antistaphylococcal activity. We engineered a lysostaphin-delivering injectable PEG hydrogel to treat Staphylococcus aureus infections in bone fractures. The injectable hydrogel formulation adheres to exposed...

https://ift.tt/2GZYNCt

Why we need to look beyond the glass transition temperature to characterize the dynamics of thin supported polymer films [Applied Physical Sciences]

There is significant variation in the reported magnitude and even the sign of Tg shifts in thin polymer films with nominally the same chemistry, film thickness, and supporting substrate. The implicit assumption is that methods used to estimate Tg in bulk materials are relevant for inferring dynamic changes in thin...

https://ift.tt/2kwfXP0

Cretaceous-Tertiary Foraminifera and Palynomorphs from Djega Section and Inferred Paleodepositional Environments, Rio Del Rey Basin, Cameroon, West Africa

Late Cretaceous-Paleocene foraminiferans and palynomorphs were recovered from the upper section of the Djega outcrop in the Rio del Rey Basin. Only a few planktonic foraminiferan species of the genera Heterohelix and Hedbergella were recovered among an assemblage dominated by calcareous and agglutinated benthonics. Marine dinocysts are curiously absent from among the palynomorph assemblage, which consists dominantly of pollen grains from land plants (angiosperms and gymnosperms) and pteridophytic spores, together with a few fungal remains. Two benthonic foraminiferal assemblages that include the Campanian-Maastrichtian Bolivina afra-Haplophragmoides talokensis and the Paleocene Anomalinoides umboniferus-Eponides pseudoelevatus are well established at this outcrop. The palynomorphs include a few typical Late Cretaceous and typical Paleogene species, while the majority are long ranging forms that straddle the Cretaceous-Tertiary boundary. The foraminiferal and palynomorph biostratigraphic distributions permitted us to recognize the succession of Campanian-Maastrichtian and Paleocene strata and the Cretaceous-Tertiary boundary for the first time in this basin. Lithofacies change from a monotonous thick pile of shales below, succeeded by sandstones, frequently alternating with mudstone, above. This indicates a general fall in sea level during the Early Paleocene earlier reported within this subregion, and the boundary marks the start of the out building of the Niger Delta which the Tertiary Rio del Rey Basin is part of. Both microfossils and lithofacies analyses aided the reconstruction of an open marine, probably middle to inner neritic shallow and transitional intertidal paleodepositional environments for the sediments exposed at this outcrop.

https://ift.tt/2sjedNq

16 Johns Hopkins Researchers among 25 to Share $7.1 Million Award To Fund Stem Cell Research

The 16 awardees from The Johns Hopkins University — representing research ranging from basic sciences to clinical sciences — are among 25 scientists who will share the $7.1 million award approved by The Maryland Stem Cell Research Commission.

https://ift.tt/2LFmbZe

Study: WIC Participation Better Among Vulnerable, Us Citizen Children Whose Mothers are Eligible for DACA

Results of a study of nearly 2,000 U.S. citizen children and their mothers add to growing evidence of the multigenerational, beneficial effects of the Deferred Action for Childhood Arrivals (DACA) immigration policy on children who are citizens, illustrating increased participation in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) among citizen children whose mothers are likely eligible for DACA.

https://ift.tt/2L5af20

Brain Scientists Identify ‘Cross Talk’ Between Neurons That Control Touch in Mice

Scientists report they have uncovered a previously overlooked connection between neurons in two distinct areas of the mammalian brain. The neurons, they say, control the sense of touch, and their experiments in mice offer insights into mapping brain circuitry that is responsible for normal and abnormal perception and movements linked to touch.

https://ift.tt/2JfTW57

Alignment of Parent- and Child-Reported Outcomes and Histology in Eosinophilic Esophagitis Across Multiple CEGIR Sites

Publication date: Available online 29 May 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Seema S. Aceves, Eileen King, Margaret H. Collins, Guang-Yu Yang, Kelley E. Capocelli, J. Pablo Abonia, Dan Atkins, Peter A. Bonis, Christina L. Carpenter, Evan S. Dellon, Michael D. Eby, Gary W. Falk, Nirmala Gonsalves, Sandeep K. Gupta, Ikuo Hirano, Kendra Kocher, Jeffrey P. Krischer, John Leung, Jessi Lipscomb, Paul Menard-Katcher, Vincent A. Mukkada, Zhaoxing Pan, Jonathan M. Spergel, Qin Sun, Barry K. Wershil, Marc E. Rothenberg, Glenn T. Furuta
BackgroundPatient-reported outcome (PRO) metrics for eosinophilic esophagitis (EoE) have been developed and validated but not used in a multicenter pediatric population or systematically aligned with histology.ObjectiveWe sought to understand 1) the potential of care-giver report to predict patient self-reported symptoms and 2) the correlation of PRO domains with histology.MethodsSubjects with EoE (n=310) and their parents participating in the Consortium of Gastrointestinal Eosinophilic Disease Researchers (CEGIR) observational clinical trial were queried for baseline patient symptoms and quality of life (QOL) using the Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0), Pediatric QOL EoE module (PedsQL-EoE) and biopsies were analyzed using the EoE histology scoring system (EoEHSS).ResultsPEESSv2.0 parent and child report aligned across all domains (r=0.68-0.73, p<0.001). PedsQL-EoE reports correlated between parents and children across ages and multiple domains (r=0.48-0.79, p<0.001). There was a tight correlation between symptoms on PEESS2.0 and their impacts QOL both on self and parent report (p<0.001). Self-reported symptoms on PEESSv2.0 (positively) and PedsQL-EoE (inversely) showed a weak correlation with proximal, but not distal, peak eosinophil counts and features and architectural tissue changes on EoEHSS (p<0.05).ConclusionsParents of children with EoE aged 3-18 years old accurately reflected their children's disease symptoms and QOL. Self- and parent-reported symptoms correlate with proximal esophageal histology. Our data suggest that parent report in young children can function as an adequate marker for self-reported symptoms and that self-reported symptoms may reflect changes in tissue histology in the proximal esophagus. These findings should be considered during clinical trials for drug development.Clinical Implications.Parent report provides an accurate surrogate marker for self-reported symptoms and QOL in pediatric EoE. Self-reported symptoms may gauge proximal esophageal histology. This should be considered in clinical trial design.

Teaser

This study shows that parent report correlates with pediatric self-report of EoE symptoms and quality of life and that self-reported symptoms correlate with histologic changes. Parent report should be considered as a self-report surrogate for future clinical trials.


https://ift.tt/2xjJMvw

A Natural Killer T cell subset that protects against airway hyperreactivity

Publication date: Available online 29 May 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savag, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu
BackgroundInfection of suckling mice with influenza virus expands a CD4^-CD8^- double negative (DN) Natural Killer T (NKT) cell subpopulation that protects the mice as adults against allergen-induced airway hyperreactivity (AHR). However, this NKT cell subset has not been characterized and the underlying mechanisms of protection remain unknown.ObjectiveWe characterized this specific NKT cell subpopulation that developed during influenza infection in neonatal mice and that suppressed the subsequent development of AHR.MethodsA cell surface marker was identified by comparing the mRNA expression profile of WT CD4⁺ NKT cells with that of suppressive Vα14 DN NKT cells. The marker-enriched NKT cell subset was then analyzed for its cytokine profile and its suppressive in vitro and in vivo abilities.ResultsWe showed that DN NKT cells with high CD38 expression produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the development of AHR through contact-dependent suppression of helper CD4 T cell proliferation. The NKT subset expanded in the lungs of neonatal mice after infection with influenza and also after treatment of neonatal mice with Nu-α-GalCer, which effectively increased DN-CD38^hi NKT cell numbers.ConclusionThese results suggest that early/neonatal exposure to infection or antigenic challenge affects subsequent lung immunity by altering the cellular composition of cells in the lung, and that some subsets of NKT cells suppress AHR. These results provide a possible mechanism by which prior infections may protect against the development of allergic asthma and may be further explore as a protective measure for young children.

Graphical abstract

Teaser

A novel NKT cell subset expands in mice after influenza infection that prevents asthma. This mechanism, which explains the protective effects afforded by childhood environmental exposures, can be reproduced by treatments that activate NKT cells.


https://ift.tt/2Jgf37k

Molecular allergy diagnostics refines characterization of children sensitized to dog dander

Publication date: Available online 29 May 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ulrika Käck, Anna Asarnoj, Hans Grönlund, Magnus P. Borres, Marianne van Hage, Gunnar Lilja, Jon R. Konradsen
BackgroundSensitization to dog dander is an important risk factor for rhino-conjunctivitis and asthma, but not sufficient for diagnosing dog allergy. Molecular allergy diagnostics offers new opportunities for refined characterization.ObjectivesTo study the association between sensitization to all presently known dog allergen components and clinical symptoms of dog allergy in children, evaluated by nasal provocation testing.Methods60 children (age 10-18 years) sensitized to dog dander extract, went through nasal provocation testing with dog dander extract. Measurement of IgE to dog dander and to Can f 1, Can f 2, Can f 3 and Can f 5 was performed with ImmunoCAP and to Can f 4 and Can f 6 with Streptavidin ImmunoCAP. An IgE level ≥ 0.1 kUA/L was considered positive.ResultsThere was an association between sensitization to an increasing number of dog allergen components and a positive nasal challenge (p=0.01). Sensitization to lipocalins (OR 6.0, CI 1.04-34.5), in particular Can f 4 (OR 6.80, CI 1.84-25.2) and Can f 6 (OR 5.69, OR 1.59-20.8) was associated with a positive nasal provocation test.Mono-sensitization to Can f 5 was related to a negative nasal provocation test (OR 5.78, CI 1.01-33.0).ConclusionSensitization an increasing number of dog allergen components, as well as sensitization to lipocalins is associated with dog allergy. Mono-sensitization to Can f 5 should not primarily be regarded as a marker for dog allergy.

Graphical abstract

Teaser

Molecular diagnostics refines characterization of dog dander sensitized children. The clinical impact of sensitization to dog allergen components was here for the first time evaluated by nasal provocation testing with dog dander extract.


https://ift.tt/2IVrdze

Identification of Galectin-3 as an Auto-Antigen in IgG4-Related Disease

Publication date: Available online 29 May 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Cory A. Perugino, Sultan B. AlSalem, Hamid Mattoo, Emanuel Della-Torre, Vinay Mahajan, Gayathri Ganesh, Hugues Allard-Chamard, Zachary Wallace, Sydney B. Montesi, Johannes Kreuzer, Wilhelm Haas, John H. Stone, Shiv Pillai
BackgroundThe antigenic trigger that drives the expansion of circulating plasmablasts and CD4⁺ cytotoxic T cells (CD4⁺ CTLs) in patients with IgG4-Related Disease (IgG4-RD) is presently unknown.ObjectiveWe sought to sequence Ig genes from single cell clones of dominantly-expanded plasmablasts and generate recombinant human monoclonal antibodies to identify relevant antigens in IgG4-RD using mass spectrometry.MethodsPaired heavy and light chain cDNAs from dominant plasmablast clones were expressed as monoclonal antibodies (mAbs) and used to purify antigens using immunoaffinity chromatography. Affinity-purified antigens were identified by mass spectrometry and validated by ELISA. Plasma levels of the antigen of interest were also determined using ELISAResultsmAbs expressed from the two dominant plasmablast clones of a patient with multi-organ IgG4-RD stained human pancreatic tissue sections. Galectin-3 was identified as the antigen specifically recognized by both mAbs. Anti-galectin-3 autoantibody responses were predominantly of the IgG4 isotype (28% of the IgG4-RD cohort, p = 0.0001) and IgE isotype (11% of IgG4-RD cohort, p = 0.009). No significant responses were seen from the IgG1, IgG2 or IgG3 isotypes. IgG4 anti-galectin-3 autoantibodies correlated with elevated plasma galectin-3 levels (p=0.001), lymphadenopathy (p=0.04), total IgG elevation (p=0.05), and IgG4 elevation (p=0.03).ConclusionAffinity chromatography using patient-derived monoclonal antibodies identifies relevant auto-antigens in IgG4-RD. IgG4 galectin-3 autoantibodies are present in a subset of IgG4-RD patients and correlate with galectin-3 plasma levels. The marked elevations of circulating IgG4 and IgE observed clinically are, at least in part, due to the development of IgG4 and IgE specific autoantibody responses.

Teaser

Using dominantly-expanded plasmablast clones, we have identified IgG4 and IgE anti-galectin-3 autoantibodies in IgG4-RD, which correlate with IgG4 levels, lymphadenopathy and over-expression of galectin-3.


https://ift.tt/2Jh5vJl

Study of Proton SBRT and Immunotherapy for Recurrent/Progressive Locoregional or Metastatic Head and Neck Cancer

Condition:   Head and Neck Cancer
Interventions:   Radiation: Proton Stereotactic Body Radiation Therapy (SBRT) (5 fractions; 3500-4500 cGy);   Radiation: Proton Stereotactic Body Radiation Therapy (SBRT) (3-5 fractions; various dose and fractionation regimens depending on treatment site).;   Drug: Nivolumab 3 mg/kg IV q2 weeks;   Radiation: Proton or Photon SBRT (3-5 fractions; various dose and fractionation regimens depending on treatment site).
Sponsor:   Mayo Clinic
Not yet recruiting

https://ift.tt/2L6ZKeK

A Phase Ib Trial of Cabozantinib in Combination With Durvalumab (MEDI4736) in Previously Treated Patients With Advanced Gastroesophageal Cancer and Other Gastrointestinal (GI) Malignancies (CAMILLA)

Conditions:   Gastric Cancer;   Esophageal Adenocarcinoma;   Hepatocellular Carcinoma;   Colorectal Cancer
Interventions:   Drug: Cabozantinib;   Drug: Durvalumab
Sponsors:   Anwaar Saeed;   AstraZeneca;   Exelixis
Not yet recruiting

https://ift.tt/2Je5tSn

Radiotherapy Concurrent With Apatinib in Advanced Soft Tissue and Bone Sarcomas of Head and Neck--RASS Study

Conditions:   Soft Tissue and Bone Tumor;   Head and Neck Cancer;   Sarcoma
Intervention:   Drug: Apatinib Mesylate
Sponsor:   Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Not yet recruiting

https://ift.tt/2L5l1W4

Dose Constraints for the Temporal Lobes of Intensity-modulated Radiotherapy Treatment Plans for Nasopharyngeal Carcinoma

Condition:   Injury; Temporal Region
Intervention:   Radiation: IMRT
Sponsors:   Jiangxi Provincial Cancer Hospital;   Sixth Affiliated Hospital, Sun Yat-sen University
Not yet recruiting

https://ift.tt/2ISMBcy

Literacy learning in a digital world

Kucirkova, N; Gillen, J; (2017) Literacy learning in a digital world. In: Goodwin, P, (ed.) The Literate Classroom. Routledge

https://ift.tt/2xobaZl

The efficiency of retrospective artifact correction methods in improving the statistical power of between-group differences in spinal cord DTI

David, G; Freund, P; Mohammadi, S; (2017) The efficiency of retrospective artifact correction methods in improving the statistical power of between-group differences in spinal cord DTI. NeuroImage , 158 pp. 296-307. 10.1016/j.neuroimage.2017.06.051 . Green open access

https://ift.tt/2IVfaWu

Whose Right to Rest? Contesting the Family Vacation in the Postwar Soviet Union

Koenker, DP; (2009) Whose Right to Rest? Contesting the Family Vacation in the Postwar Soviet Union. Comparative Studies in Society and History , 51 (2) pp. 401-425. 10.1017/S0010417509000176 . Green open access

https://ift.tt/2IWBICd

Eimeria spp. in captive-reared corncrakes (Crex crex): results of a GeneScan assay consistent with high prevalence of infection and extra-intestinal life stages

Serna, H; Pocknell, A; Sainsbury, AW; Peniche, G; Blake, DP; Beckmann, KM; (2018) Eimeria spp. in captive-reared corncrakes (Crex crex): results of a GeneScan assay consistent with high prevalence of infection and extra-intestinal life stages. Avian Pathology 10.1080/03079457.2018.1451621 . (In press).

https://ift.tt/2IT0bfU

Understanding platform competition through simulation: a research outline

Papachristos, G; van de Kaa, G; (2018) Understanding platform competition through simulation: a research outline. Technology Analysis & Strategic Management 10.1080/09537325.2018.1473850 . (In press).

https://ift.tt/2J10QaX

The curriculum arguments of Michael Young and John White

Reiss, MJ; (2017) The curriculum arguments of Michael Young and John White. In: Guile, D and Lambert, D and Reiss, MJ, (eds.) Sociology, Curriculum Studies and Professional Knowledge: New perspectives on the work of Michael Young. (pp. 121-131). Routledge: Abingdon, United Kingdom.

https://ift.tt/2LFjqYe

Language documentation and archives in South America

Seifart, F; Drude, S; Franchetto, B; Gasche, J; Golluscio, L; Manrique Cordeje, ME; (2008) Language documentation and archives in South America. Language Documentation & Conservation , 2 (1) pp. 130-140. Green open access

https://ift.tt/2IZ3gqS

Radical education

Suissa, J; Charkin, E; (2017) Radical education. In: Gordon, U and Kinna, R, (eds.) Routledge handbook of radical politics. Routledge: London, United Kindom. (In press).

https://ift.tt/2LHe6U6

Is it Advisable to Rehabilitate and Release Owls with Monocular Vision?

Zimmerman, J; Sainsbury, AW; Williams, DL; (2018) Is it Advisable to Rehabilitate and Release Owls with Monocular Vision? International Journal of Avian & Wildlife Biology , 3 (1) , Article 00044. 10.15406/ijawb.2018.03.00044 . Green open access

https://ift.tt/2xnhobZ

Reducing the exposure of the tonsillar fossa does not impact postoperative pain levels in children undergoing tonsillectomy: A double-blind randomized controlled trial

Publication date: August 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 111
Author(s): Marco Aurélio Fornazieri, Edson Satoshi Miyazato, Henrique Massamiti Yamamoto, Paulo de Lima Navarro, Fábio de Rezende Pinna, Richard Louis Voegels
BackgroundIt is not established whether reducing the exposure of the tonsillar fossa would be an effective strategy for postoperative pain relief among the pediatric population submitted to tonsillectomy. We assessed the impact of closing this region using absorbable sutures on pain, on the resumption of normal diet and on the healing process until seven days after surgery.MethodsRandomized, double-blind, controlled trial comparing postoperative pain in 132 children between the ages of 5 and 12 years undergoing tonsillectomy having bilateral closure, unilateral closure or non-closure of the tonsillar fossa.ResultsNo differences in pain levels were reported both at discharge and on postoperative day 7. The day of resumption of normal diet was similar in all patients. Less granuloma and edema of the uvula were noted in patients with non-closure of the tonsillar fossa.ConclusionThese results showed that reducing the exposure of the tonsillar fossa after the removal of the palatine tonsils was not an effective method for postoperative pain relief in children. Moreover, its closure was associated with slower healing.



https://ift.tt/2slhqva

Infection of the spheno-occipital synchondrosis: A morbid complication following adenoidectomy

Publication date: August 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 111
Author(s): Amy E. Wagenaar, David M. Mirsky, Nicholas V. Stence, Todd M. Wine, Kenny H. Chan
Two 2-year-old males presented post-operatively following adenoidectomy with persistent fever and neck stiffness. After multiple office visits, both patients were admitted and found to have a widened spheno-occipital synchondrosis and other imaging findings indicative of skull base osteomyelitis. Treatment with antibiotics allowed for recovery with good long-term outcomes. Infection involving the spheno-occiptal synchondrosis is rare and its circuitous presentation of these two children no doubt led to delayed diagnosis.



https://ift.tt/2kz2juQ

Sex Hormone Levels Alter Heart Disease Risk in Older Women

In an analysis of data collected from more than 2,800 women after menopause, Johns Hopkins researchers report new evidence that a higher proportion of male to female sex hormones was associated with a significant increased relative cardiovascular disease risk.

https://ift.tt/2IVHtnO

Chronic Rhinosinusitis in Children: Pathophysiology, Evaluation, and Medical Management

Abstract

Purpose of Review

Pediatric chronic rhinosinusitis (CRS) is a common disorder that carries significant morbidity. The diagnosis requires sinus symptoms that persist despite standard medical therapy greater than 3 months. Viral infections, allergies, and anatomic differences in children lead to chronic obstruction of the osteomeatal complex.

Recent Findings

Chronic rhinosinusitis as a diagnosis is a conglomeration of multiple phenotypes and endotypes. As such, the diagnosis and management are complex. New survey studies provide some consensus on prevalence and management of this disease in children.

Summary

In this review, we highlight the differential diagnosis of pediatric CRS, including non-eosinophilic/infectious variants, eosinophilic variants with and without nasal polyps, allergic fungal sinusitis, aspirin-exacerbated respiratory disease, primary immunodeficiency, and disorders of mucociliary clearance. Further, we detail treatment options that should be considered. Finally, we feature emerging potential treatment options of CRS, including anti-immunoglobulin E, interleukin-5, and interleukin-4 receptor alpha subunit.

https://ift.tt/2kwGbkz

Transwindow Suture Technique for Pseudocyst of Pinna

Abstract

Pseudocyst or seroma of the pinna is the accumulation of serous fluid between the perichondrium and cartilage of pinna. Though there are several surgical techniques in the treatment of seroma, recurrence is common. The aim and objective of this preliminary study is to present and discuss a novel technique of treating pseudocyst of pinna which is practiced at Karwar Institute of Medical sciences. A prospective study was done with a novel procedure "Transwindow suture technique" for the treatment of pseudocyst of pinna in four patients. Three of the four patients had a very good results without any recurrence. One patient had a small quantity of recollection due to premature closure of the skin window which was successfully corrected. In this preliminary study we had encouraging results in the treatment of pseudocyst of pinna. A large scale prospective study would demonstrate the effectiveness of this procedure.

https://ift.tt/2xojhFd

Exploring Conceptions and Discourses of Gender, Sexuality and Pregnancy Amongst Mexican Adolescents

Weil-Behar, Miriam; (2016) Exploring Conceptions and Discourses of Gender, Sexuality and Pregnancy Amongst Mexican Adolescents. Doctoral thesis (M.Phil), UCL (University College London).

https://ift.tt/2kBpog5

Deep D-bar: Real time Electrical Impedance Tomography Imaging with Deep Neural Networks

Hamilton, SJ; Hauptmann, A; (2018) Deep D-bar: Real time Electrical Impedance Tomography Imaging with Deep Neural Networks. IEEE Transactions on Medical Imaging 10.1109/TMI.2018.2828303 . (In press). Green open access

https://ift.tt/2ssQQk3

Psychological models of pain

Williams, ACDC; (2017) Psychological models of pain. In: The Routledge Handbook of Philosophy of Pain. (pp. 143-153).

https://ift.tt/2kwWjm1

Clinicians' perception of the preventability of inpatient mortality

Nash, R; Srinivasan, R; Kenway, B; Quinn, J; (2018) Clinicians' perception of the preventability of inpatient mortality. International Journal of Health Care Quality Assurance , 31 (2) pp. 131-139. 10.1108/IJHCQA-06-2016-0083 . Green open access

https://ift.tt/2skZq44

Switch in photocatalytic reaction selectivity: The effect of oxygen partial pressure on carbon-carbon bond dissociation over hydroxylated TiO2(1 1 0) surfaces

Harrison, G; Katsiev, K; Alsalik, Y; Thornton, G; Idriss, H; (2018) Switch in photocatalytic reaction selectivity: The effect of oxygen partial pressure on carbon-carbon bond dissociation over hydroxylated TiO2(1 1 0) surfaces. Journal of Catalysis , 363 pp. 117-127. 10.1016/j.jcat.2018.04.015 . (In press).

https://ift.tt/2seHwAC

Relative sea-level change in western New Guinea recorded by regional biostratigraphic data

Gold, DP; White, LT; Gunawan, I; BouDagher-Fadel, MK; (2017) Relative sea-level change in western New Guinea recorded by regional biostratigraphic data. Marine and Petroleum Geology , 86 pp. 1133-1158. 10.1016/j.marpetgeo.2017.07.016 .

https://ift.tt/2H1ZcUK

Effectiveness of interventions for diagnosis and treatment of tuberculosis in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review

Heuvelings, CC; de Vries, SG; Greve, PF; Visser, BJ; Bélard, S; Janssen, S; Cremers, AL; ... Grobusch, MP; + view all Heuvelings, CC; de Vries, SG; Greve, PF; Visser, BJ; Bélard, S; Janssen, S; Cremers, AL; Spijker, R; Shaw, B; Hill, RA; Zumla, A; Sandgren, A; van der Werf, MJ; Grobusch, MP; - view fewer (2017) Effectiveness of interventions for diagnosis and treatment of tuberculosis in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review. The Lancet Infectious Diseases , 17 (5) e144-e158. 10.1016/S1473-3099(16)30532-1 . Green open access

https://ift.tt/2sgG6WA

Editorial Board

https://ift.tt/2IUDaF7

Thoracic oesophageal cancer as a cause of stridor: a literature review

An 83-year-old woman, with a background of treated squamous cell oesophageal cancer, presented with a 3-week history of stridor. Of note, the patient had no risk factors for oesophageal cancer other than age. Clinical examination was unremarkable apart from stridor. Laboratory investigations, including arterial blood gas on room air, were unremarkable. Radiological examination revealed a 4.5x3.5x3.6 cm mass involving the posterior trachea and invading the tracheal orifice. Oesophagogastroduodenoscopy and rigid bronchoscopy confirmed an extensive tumour arising from the lower oesophagus and invading the trachea, causing 90% airway obstruction for a 6 mm length ending 1.5 cm above the carina. Biopsy revealed a poorly differentiated carcinoma with foci of squamous cell carcinoma. Unfortunately, the patient passed away 2 months after palliative tracheal stent placement.

https://ift.tt/2L3hmI9

Benign acute myositis in an adult patient

The benign acute childhood myositis presents as a marked and painful oedema of leg muscles in the days following a viral illness. This disease is often considered as occurring only in children. We report the case of a 32-year-old patient who presented with severe pain and oedema of both legs associated with motor deficit of lower extremities. He suffered from a grippal syndrome for 4 days. Creatine kinase blood level rose up to 39 394 IU/L (n<200) and a muscle biopsy of left tibialis anterior found necrosisand regeneration of myocytes without inflammatory infiltrates. All clinical and paraclinical abnormalities spontaneously disappeared in a few days. This case illustrates that a disorder similar to benign acute childhood myositis may occur in adult patients. Muscle biopsy might be avoided in typical cases because of the favourable evolution.

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Keratinising squamous cell metaplasia: when is it safe to stop looking?

Keratinising squamous cell metaplasia (KSCM) is an uncommon diagnosis in the West. Patients typically present with lower urinary tract symptoms: haematuria (visible and non-visible), dysuria, urgency and frequency. Investigation is rigid cystoscopy. Abnormal bladder wall tissue should be resected and biopsies sent for histopathology to confirm KSCM. This is a preneoplastic condition with strong associations with squamous cell carcinoma. Due to a significant lag time, annual cystoscopy with multiple biopsies is recommended.

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Acute non-cardiogenic pulmonary oedema due to contralateral pulmonary re-expansion after thoracentesis: an uncommon complication

Description 

An 82-year-old man presented with hypoxaemic respiratory insufficiency due to left-sided pneumonia and lung atelectasis, with a large, long-standing (>7 days) ipsilateral pleural effusion (figure 1A,B). Four hours after draining 1500 mL of transudative pleural fluid, the patient had worsening hypoxaemia and increasing supplemental oxygen necessity (fractional inspired oxygen 60% with high-flow face mask). The left lung had expanded, as noted by normal vesicular lung sounds, while diffuse crackles were exhibited on the right side. The chest radiograph (figure 1C) shows asymmetrical diffuse alveolar opacity in the right lung field, which in this setting relates to non-cardiogenic pulmonary oedema after contralateral pulmonary re-expansion. After 12 days of conservative treatment, the patient was well, his left lung was expanded and his right-sided oedema had completely resolved (figure 1D), with no need for supplemental oxygen.

Figure 1

(A) Chest X-ray showing a left-sided pneumonia and...

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Gastric duplication cyst with elevated CEA level: a case report

Abstract

Gastrointestinal tract duplications are congenital malformations rarely seen in adulthood. Gastric duplications (GD) represent 2–9% of it. Malignant transformation of GD is a rare complication described in the literature. We present the case of a 43-year-old man, who presented an abdominal mass and an elevated CEA level. A total gastrectomy was performed and the histological examination described a gastric duplication cysts (GDC) without malignant transformation. It is not the first case of elevation of CEA in GDC without evidence of malignancy described in the literature. Some authors think that GDC are premalignant lesions that envolve with the time to carcinomas. It is recommend that once the GDC is diagnosed to remove surgically the entire cyst even if the patient is asymptomatic.

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Bleb formation in small unruptured intracranial aneurysm as a predictor of early rupture

Abstract

Small unruptured aneurysms are thought to have a low risk of rupture, but the management of such lesions is still controversial. A 73-year-old man with a small anterior communication artery aneurysm, 4 mm in diameter, while on follow-up, developed an aneurysmal subarachnoid hemorrhage 2 weeks after the detection of a newly emerged bleb on the surface of the aneurysm. In conclusion, the formation of a bleb should be considered as a warning sign of an impending rupture, and treatment should be provided even for patients with small aneurysms.

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Metastatic lobular breast carcinoma to the pancreas: a case report

Abstract

We report a case of a 72-year-old female, with an extensive breast cancer history, who presented with abdominal pain to her general practitioner. Cross-sectional imaging demonstrated a lesion in the head of pancreas, which was not amenable to curative resection. Percutaneous biopsy was obtained, which demonstrated metastatic lobular breast cancer. This rare case highlights how previous medical histories may assist in final pathological diagnosis.

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Pharmacobezoar—a rare case presented as gastric outlet obstruction

Abstract

BEZOARS are retained concretions of indigestible foreign material that accumulate and conglomerate in the gastrointestinal tract, most commonly in the stomach. Prevalence of bezoar is 0.4%. Bezoars are classified in four categories: phytobezoars; trichobezoars; pharmacobezoars; lactobezoars. A 58-year-old man admitted with complains of pain abdomen and recurrent vomiting since last 3 months. Upper GI endoscopic biopsy reported—chronic gastritis with very occasional non-caseating epitheloid granuloma in lamina propria, no evidence of neoplasia? Crohn's disease. Keeping Crohn's as diagnosis patient was given mesalamine 400 mg tid by gastrophyscian. But patient did not respond so the patient was advised surgical management. Repeat UGI endoscopy revealed multiple pills (mesalamine) in the stomach with gastric outlet obstruction (GOO). Around 40 pills were extracted with the help of flower basket, and then patient develope GOO and underwent Laparoscopic gastrojejunostomy and truncal vagotomy.

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Rare case of bleeding nipple hemangioma in a lactating mother

Abstract

Hemangiomas of nipple of the breast are rare lesions and are limited to case reports in the literature. Such pathology in a lactating mother are clearly a hindrance preventing the child from breastfeeding with its benefits. We report a rare case of a bleeding nipple hemangioma in a 24 years old lactating mother with the clinical, imaging and histopathological findings.

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Biliary pancreatitis in a duplicate gallbladder: a case report and review of literature

Abstract

Duplicated gallbladder is a rare congenital anomaly that require special attentions due to its clinical, surgical and diagnostic difficulties. We present a case of a 39-year-old female patient with a duplicated gallbladder who presented with an acute biliary pancreatitis, a case to our knowledge is the first in the literature. A double gallbladder in an abdominal ultrasonography was doubtful, thus a computed tomography scan, a magnetic resonance cholangiopancreatography and an endoscopic retrograde cholangiopancreatography were done that confirmed the double gallbladder. A laparoscopic cholecystectomy with an intraoperative cholangiography was performed safely two months after the acute attack. The histopathological report revealed a Y-shaped type 1 double gallbladder according to the Harlaftis et al. classification.

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Effects of Progressive Additional Lenses on Binocular Vision in Children with Pseudophakia

Binocular vision may be compromised in children after unilateral cataract surgery because the distances at which clear vision is present are different for the two eyes. We believe that wearing progressive additional lenses can be effective in improving the binocular vision in children with pseudophakia.
Case Rep Ophthalmol 2018;9:304–309

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Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for non-small cell lung cancer patients

Abstract

Adoptive cell therapy (ACT) of tumor infiltration lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Due to the fact that metastatic lung cancer has proven to be susceptible to immunotherapy and possesses a high mutation burden, which makes it responsive to T cell attack, we explored the feasibility of TIL ACT in non-small cell lung cancer (NSCLC) patients. Multiple TIL cultures were isolated from tumor specimens of five NSCLC patients undergoing thoracic surgery. We were able to successfully establish TIL cultures by various methods from all patients within an average of 14 days. Fifteen lung TIL cultures were further expanded to treatment levels under good manufacturing practice conditions and functionally and phenotypically characterized. Lung TIL expanded equally well as 103 melanoma TIL obtained from melanoma patients previously treated at our center, and had a similar phenotype regarding PD1, CD28, and 4-1BB expressions, but contained a higher percent of CD4 T cells. Lung carcinoma cell lines were established from three patients of which two possessed TIL cultures with specific in vitro anti-tumor reactivity. Here, we report the successful pre-clinical production of TIL for immunotherapy in the lung cancer setting, which may provide a new treatment modality for patients with metastatic NSCLC. The initiation of a clinical trial is planned for the near future.

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Comparison of Duke Activity Status Index with cardiopulmonary exercise testing in cancer patients

Abstract

Purpose

The Duke Activity Status Index (DASI), a patient-administered questionnaire, is used to quantify functional capacity in patients undergoing cancer surgery.

Methods

This retrospective cohort study assessed whether the DASI was accurate in predicting peak oxygen consumption (pVO₂) that was objectively measured using cardiopulmonary exercise testing (CPET) in 43 consecutive patients scheduled for elective major cancer surgery at a tertiary cancer centre. The primary outcome measured the limits of agreement between DASI-predicted pVO₂ and actual measured pVO₂.

Results

The study population was elderly (median 63 years, interquartile range 18), 58% were male, with the majority having intraabdominal cancer surgery. Although the DASI scores were statistically related to the measured pVO₂ (N = 43, adjusted R² = 0.20, p = 0.002), both the bias (8 ml kg^− 1 min^− 1) and 95% limits of agreement (19.5 to − 3.4 ml kg^− 1 min^− 1) between the predicted and measured pVO₂ were large. Using some of the individual components, recalibrating the intercept and regression coefficient of the total DASI score did not substantially improve its ability to predict the measured pVO₂.

Conclusion

In summary, both the limits of agreement and bias between the measured and DASI-predicted pVO₂ were substantial. The DASI-predicted pVO₂ based on patient's assessment of their functional status could not be considered a reliable surrogate of measured pVO₂ during CPET for the population of patients pending major cancer surgery and cannot, therefore, be used as a triage tool for referral to CPET centres for objective risk assessment.

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