The effects of venous ensheathment on facial nerve repair in the rat

Objective

To investigate the protective effect of autologous venous ensheathment on sutured rat facial nerve and to test whether the ensheathment could improve the functional recovery of repaired nerve and accuracy of axonal growth.

Study Design

In vivo study.

Methods

Forty-six rats were examined, with six rats serving as normal controls and 40 receiving facial nerve transection and suture repair (SR) or transection and suture repair with an additional venous ensheathment (VE). The rats were then subjected to functional testing, histological assessment of nerve specimens, or retrograde tracing, respectively.

Results

At the postoperative day (POD) 60, the venous ensheathment showed no adhesion at the surrounding tissues. No significant difference in neuroma formation was found between the two surgical manipulations (SR and VE groups) (P < 0.05). Retrogradely labeled motoneurons in facial nuclei were extremely disorganized after the facial nerve undertook surgical manipulation. In all manipulated groups, double retrogradely labeled neurons, indicative of aberrant axonal branching during regeneration, could be observed after peripheral manipulation across all time points. With the two facial surgical manipulations, the average count of double-labeled neurons at POD 60 was significantly less than at POD 21 (P < 0.05).

Conclusion

Autologous venous ensheathment could not help with the functional recovery of facial nerve or improve the accuracy of axonal regeneration. Further studies are warranted to elucidate the effects of venous ensheathment in other motor and sensory nerve models.

Level of Evidence

NA. Laryngoscope, 2017

http://ift.tt/2kYo6Kb

Pepsin as a biomarker for laryngopharyngeal reflux in children with laryngomalacia

Objectives/Hypothesis

Laryngomalacia is a common cause of newborn stridor. Laryngopharyngeal reflux (LPR) has been associated with laryngomalacia. Although pepsin, a component of LPR, has been associated with inflammatory diseases of the aerodigestive tract, its presence in the airways of laryngomalacia patients is unknown.

Study Design

Prospective case-control study comparing patients under age 3 years with laryngomalacia to children without laryngomalacia.

Methods

Children less than 3 years old undergoing supraglottoplasty for laryngomalacia or surgery unrelated to the airway, without a history of laryngomalacia, reflux, or respiratory disease, were offered enrollment. Supraglottic lavage samples (3 mL) were obtained from all subjects. Two-millimeter arytenoid biopsies were collected from laryngomalacia patients. Pepsin Western blot and enzyme-linked immunosorbent assay were performed.

Results

Ten laryngomalacia and five control subjects were enrolled. Pepsin was detected in lavages of laryngomalacia patients (8/10) but absent in controls (0/5; P = .007). Pepsin was observed more frequently in lavages (8/10) than biopsies (4/10; P = .046) of laryngomalacia subjects. Higher median pepsin concentration was observed in laryngomalacia than control lavages (P = .025).

Conclusions

Pepsin in supraglottic specimens demonstrated an association with laryngomalacia, supporting a role for refluxed pepsin in laryngomalacia. These data corroborate previous work implicating pepsin in inflammatory diseases of the upper airways. Further studies are warranted to investigate the contribution of pepsin to the pathophysiology of laryngomalacia.

Level of Evidence

3b. Laryngoscope, 2017

http://ift.tt/2m6G2He

The current status of human laryngeal transplantation in 2017: A state of the field review

Objectives

Human laryngeal allotransplantation has long been contemplated as a surgical option following laryngectomy, but there is a paucity of information regarding the indications, surgical procedure, and patient outcomes. Our objectives were to identify all human laryngeal allotransplants that have been undertaken and reported in the English literature and to evaluate the success of the procedure.

Data Sources

MEDLINE, Embase, Current Index to Nursing and Allied Health Literature, Web of Science and Scopus, and the Gray literature.

Review Methods

A comprehensive search strategy was undertaken across multiple databases. Inclusion criteria were case reports of patients who had undergone human laryngeal allotransplantation. Information regarding indications, operative techniques, complications, graft viability, and functional outcomes were extracted.

Results

A total of 5,961 articles, following removal of duplicates, matched the search criteria and were screened, with five case reports relating to two patients, ultimately fulfilling the entry criteria.

Conclusions

Two laryngeal transplants have been reported in the medical literature. Although both patients report improved quality of life relating to their ability to communicate with voice, further research is necessary to shape our understanding of this complicated operation, its indications, and its functional outcomes. Laryngoscope, 2017

http://ift.tt/2ltXyCo

Clinical effect of intratympanic dexamethasone injection in acute unilateral tinnitus: A prospective, placebo-controlled, multicenter study

Objective

The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection (ITDI) in acute tinnitus of presumed cochlear origin.

Study Design

A prospective, randomized, placebo-controlled, double-blinded, multicenter study.

Methods

Between August 2013 and December 2015, 54 patients with unilateral tinnitus were enrolled at four different centers. Patients were assigned either to an ITDI (n = 27) or an intratympanic normal saline injection (ITNI; n = 27) group through block randomization. Intratympanic injections were administered four times over 2 weeks. At 4 weeks after initial injection, we analyzed the improvement rates of tinnitus using the tinnitus handicap Inventory (THI) and visual analogue scale (VAS) for loudness, awareness, and annoyance. We defined improvement as the reduction of more than 7 points or of more than 20% in the final THI score compared to the initial THI score.

Results

The initial mean hearing thresholds and VAS and THI scores of the two groups did not differ significantly. At 4 weeks after initial injection, the mean VAS and THI scores of both groups had significantly reduced. However, the improvement rate did not differ significantly between the groups (ITDI, 51.9%; ITNI, 59.3%).

Conclusion

The results indicate that ITDI might not be more effective than ITNI for the treatment of acute unilateral tinnitus. Therefore, ITDI should not be considered as the main treatment for patients presenting with acute tinnitus as the primary symptom.

Level of Evidence

1b. Laryngoscope, 2017

http://ift.tt/2m6KGFl

Customized software to optimize circumferential pharyngoesophageal free flap reconstruction

http://ift.tt/2ltRM3n

Laboratory assessment of sudden sensorineural hearing loss: A case-control study

Objectives/Hypothesis

Sudden sensorineural hearing loss (SSHL) is an otologic emergency that affects five to 30 subjects per 100,000/year. The cause of SSHL remains unknown or uncertain in 70% to 90% of cases, and treatment decisions are usually made without knowing the etiology.

Study Design

Prospective case-control study.

Methods

One hundred thirty-one idiopathic SSHL patients were recruited from January 2014 to June 2015 in concordance with the Statements of Clinical Practice Guideline and divided into groups according to the disease severity. A clinical laboratory assessment was completed on blood samples collected from SSHL patients and control subjects. Multivariable regression analysis was performed to investigate the association between laboratory data and SSHL basis.

Results

Only a few SSHL patients were positive for autoimmunity or viral infection. Statistically significant (P < .05) higher levels of blood glucose, glycated hemoglobin (HbA1C), lipoprotein (a), and factor VIII were found in SSHL patients compared to controls. Furthermore, blood glucose, HbA1C, uric acid, factor VIII, and homocysteine were significantly associated to disease severity.

Conclusions

Gluco-metabolic, lipidic, and coagulative laboratory data support the vascular hypothesis for SSHL and its severity.

Level of Evidence

3b Laryngoscope, 2016

http://ift.tt/2m6IIox

Quality of life of patients who underwent aesthetic rhinoplasty: 100 cases assessed with the Glascow Benefit Inventory

Objectives/Hypothesis

The aim of the present study is to assess the long-term effect of classic rhinoplasty on patients' quality of life.

Study Design

Outcomes research.

Methods

The study included 100 operated patients; there were 34 males and 66 females. The ages ranged between 23 and 57 years old, with a mean of 36.4 years. A minimum of 3 years between the operation and the study was selected to assess the long-term effect of the operation on the patients' quality of life and exclude any short-term impressions. The time elapsed between surgery and the time of the study ranged from 3 to 13 years, with a mean of 6.8 years. Patients were assessed using the Glasgow Benefit Inventory, which has been proven valid and reliable in ear, nose, and throat interventions.

Results

From the 100 patients included in the study, 92 reported improvement in their quality of life due to the operation and only eight worsening. In the social support subscale, 97 patients reported better quality of life, and only three patients reported worse quality of life. The patients' overall life markedly improved, reaching a mean of 80% in the Glasgow Benefit Inventory.

Conclusions

The present long-term study using a validated and reliable instrument concludes that rhinoplasty improves the quality of life of patients in all sectors.

Level of Evidence

2c Laryngoscope, 2017

http://ift.tt/2ltM6GK

Compound motor action potential duration and latency are markers of recurrent laryngeal nerve injury

Objective

Compound motor action potential (CMAP) can quantitatively evaluate innervation following injury to the recurrent laryngeal nerve (RLN) in canines. CMAP duration (the total time of CMAP) and latency (the time between the nerve impulse and the onset of action potentials) have not been assessed following RLN injury.

Study Design

Animal study.

Methods

Twelve canine hemilaryngeal preparations were investigated. Baseline CMAP duration and latency were derived. Group A (n = 5) underwent RLN stretch injury, and group B (n = 7) underwent RLN transection/repair. The change in CMAP duration and latency was assessed between the baseline and 6-month measurements using receiver operator characteristic (ROC) curves for each group individually and combined.

Results

Six months following injury, transection/repair injuries had the most significant increase in CMAP duration (2.8 ± 0.6 ms vs. 4.2 ± 0.8 ms, difference 1.4 ms 95% confidence interval [CI]: 0.43 to 2.40) and latency (2.6 ± 0.5 ms vs. 5.6 ± 1.5 ms, difference 3.0 ms 95% CI: 1.65 to 4.38). Stretch injuries also caused an increase in CMAP duration (2.3 ± 0.8 ms vs. 3.0 ± 0.6 ms, difference 0.7 ms 95% CI: −0.49 to 1.77) and latency (2.5 ± 0.8 ms vs. 4.7 ± 1.5 ms, difference 2.3 95% CI: 0.76 to 3.80). Using ROC curves, CMAP duration and latency differentiated between the baseline control and RLN injury at 6 months (area under the curve = 0.78 and 0.98, respectively).

Conclusion

CMAP duration and latency are both quantitative measures that may have clinical utility as markers of RLN injury. CMAP latency had superior discrimination between injured and uninjured RLNs. Increased CMAP duration and latency may be explained by incomplete myelination and focal conduction block.

Level of Evidence

NA. Laryngoscope, 2017

http://ift.tt/2m6I22v

The repeatability of tests of eustachian tube function in healthy ears

Objectives/Hypothesis

Many objective tests of eustachian tube (ET) function have been devised for clinical and research use but they have not been directly compared or characterized. As a first step to identifying tests to incorporate into an outcome set for ET dysfunction, we assessed repeatability of a panel of eight of these tests in healthy ears.

Study Design

Comparison of eight tests of ET function.

Methods

The following tests were investigated in combination with Valsalva, Toynbee, swallow, or sniff maneuvers: 1) patient-reported ET opening, 2) observed tympanic membrane movement, 3) continuous impedance, 4) canal manometry, 5) sonotubometry, 6) nine-step test, 7) tubomanometry, and 8) tympanometry at rest. Forty-two healthy volunteers were recruited. Each test was performed in 20 different ears and repeated immediately three times in each cycle, with four cycles performed at 20-minute intervals. Repeatability of detected ET opening was compared using the intraclass correlation coefficient (ICC).

Results

Mean ET opening rate with each test ranged from 30% to 95%. Variation in detection of ET opening was less when tests were repeated immediately (ICC = 0.61) when compared to between cycles (ICC = 0.49), suggesting there may be significant changes in ET function in the short term. Tubomanometry was the only test to combine a detected ET opening rate of >85% and substantial agreement of results (ICC >0.61) between test cycles.

Conclusions

Tubomanometry was the most reliable test at detecting ET opening. When tests of ET function are used in clinical practice, they should be performed more than once to gain a more reliable result.

Level of Evidence

3b Laryngoscope, 2017

http://ift.tt/2lmu8ro

Impacts of disease severity on postoperative complications in children with sleep-disordered breathing

Objectives/Hypothesis

To investigate the effects of diseases severity on postoperative complications following adenotonsillectomy (T&A) in children with sleep-disordered breathing (SDB).

Study Design

Retrospective study.

Methods

Children aged <18 years were enrolled and underwent T&A for treating SDB. Polysomnography was used to classify the disease severity: primary snoring (apnea-hypopnea index [AHI] <1), mild (AHI = 1–5), moderate (AHI = 5–10), and severe obstructive sleep apnea [OSA] (AHI ≥10). Postoperative bleeding was graded using a severity scale (level I, self-reported bleeding; level II, requiring inpatient admission; level III, requiring reoperation). Primary bleeding is defined as hemorrhage occurring within the initial 24 postoperative hours. Perioperative respiratory complications are defined as oxygen saturation of less than 90%, 92%, or 95% in the recovery room. Major respiratory complications include laryngospasm, pulmonary edema, pneumonia, and intubation at recovery stage.

Results

A total of 610 children were included, of whom 42 (6.9%), eight (1.3%), and six (1.0%) children showed levels I, II, and III postoperative bleeding, respectively. Only one child had primary bleeding. The incidence and timing of postoperative bleeding did not differ significantly for children with different OSA severities. The rate of perioperative respiratory complications ranged from 1.6% to 14.3% on the basis of their definitions. The Cochran-Armitage test supported the trend that perioperative respiratory complications increase with the AHI. Six children developed major respiratory complications, which were not significantly associated with OSA severity.

Conclusions

Children with severe OSA have increased risks of perioperative respiratory complications. However, OSA severity does not influence major respiratory complications or postoperative bleeding in children.

Level of Evidence

4 Laryngoscope, 2017

http://ift.tt/2kYmfol

Intranasal trigeminal function in patients with empty nose syndrome

Objectives/Hypothesis

Trigeminal nerve mediates the perception of nasal airflow. This study examines whether impaired intranasal trigeminal function is a part of the paradoxical nasal obstruction sensation in patients with empty nose syndrome (ENS).

Study Design

Prospective case-control study in a tertiary hospital.

Methods

Three groups were examined: 1) ENS patients with previous bilateral near total inferior turbinectomy, 2) patients who underwent near total inferior turbinate removal (ITR) without ENS symptoms, and 3) control participants. All participants examined with active anterior rhinomanometry, olfactory testing (extended Sniffin' Sticks test), and trigeminal testing (lateralization task using menthol and odorless solvent).

Results

Seventy-one participants were included (21 ENS patients, 18 ITR patients, and 31 controls). Analyses revealed that ENS patients had significantly lower scores on trigeminal lateralization testing than the ITR group and controls. The ENS group had also significantly lower scores in olfactory testing than controls. No statistical differences were found in rhinomanometry between groups. The gender factor was not associated with the chemosensory testing; however, this was not the case with the age factor, as trigeminal test results were negatively correlated.

Conclusions

This study demonstrates significantly impaired intranasal trigeminal function in ENS patients when compared with ITR patients and controls. Further prospective studies are needed to clarify the role of preoperative trigeminal function of these patients and the contribution of surgery to this impairment.

Level of Evidence

3b. Laryngoscope, 2017

http://ift.tt/2lmAAyD

Scoping review: Awareness of neurotoxicity from anesthesia in children in otolaryngology literature

Objective

Review otolaryngology literature for awareness of neurotoxicity from general anesthesia in children. Recently, there has been increasing focus in anesthesia literature on the long-term effects of general anesthesia on neurodevelopment. Multiple animal models have demonstrated evidence of neurotoxicity from both inhalational and intravenous anesthetics. Cohort studies also have revealed modestly increased risk of adverse neurodevelopmental outcomes in children exposed to a single episode of general anesthesia prior to 3 to 4 years of age, with stronger evidence for multiple exposures in this age range. Otolaryngologists may subject children to general anesthesia via procedures or tests, including computed tomography, magnetic resonance imaging, and auditory brainstem response.

Data Sources

PubMed, Embase, Scopus, and Web of Science Review.

Methods

A scoping review using the above databases was performed limited to January 2005 through December 2015. Articles were screened and reviewed based on predefined inclusion and exclusion criteria.

Results

Initial search generated 3,909 articles. After 72 full text articles were reviewed, only seven articles mentioned neurotoxicity as a risk of general anesthesia in pediatric patients.

Conclusion

Despite the high volume of pediatric otolaryngologic procedures performed annually, there remains limited awareness in our literature discussing neurotoxicity as an outcome. Prospective data from anesthesia literature is still pending; therefore, specific recommendations cannot be made at this time. Otolaryngologists should be aware of the concerns and work toward defining elective procedures, combining surgical procedures with other procedures or imaging, and reassessing the timing and frequency of various interventions under general anesthesia in young children. Laryngoscope, 2017

http://ift.tt/2kYwhWB

Can contaminated water be rendered safe for nasal saline irrigations?

Objectives/Hypothesis

To compare sterile water to three methods of sterilization (carbon filtration, boiling, and ultraviolet [UV] light) for preparation of nasal saline irrigants free of bacterial and amebic contaminants.

Study Design

Bench-top translational research and cost comparison.

Methods

Sterile water was compared to common sterilization methods. Sterile water was contaminated with known concentrations of Staphylococcus aureus, Pseudomonas aeruginosa, Moraxella catarrhalis, Acinetobacter baumannii, Klebsiella pneumonia, Legionella pneumophila, and Naegleria fowleri. Test samples were subjected to boiling, carbon filtration, or ultraviolet light (UV) and then cultivated on appropriate media. Controls included samples of sterile water (negative control) and untreated test samples (positive control).

Results

Carbon filtration reduced but did not eliminate the number of organisms present in test samples. Boiling test samples for 5 minutes and UV light treatment resulted in sterilization of all organisms. Negative (sham contaminated) samples produced no growth, whereas positive (untreated) samples grew numerous organisms as expected. A cost comparison between bottled water and UV water sterilization (with SteriPEN Ultra) became equal in less than 2 years of consistent use.

Conclusions

Carbon filtration reduces contamination but does not sterilize water and is thus unsafe for preparation of nasal saline irrigant. Boiling and UV treatment resulted in sterilization and are equivalent to purchased sterile water. Ultraviolet treatment was found to be safe, convenient, and a cost-effective alternative to purchased sterile water.

Level of Evidence

NA Laryngoscope, 2017

http://ift.tt/2lmxESy

The feasibility of NBI in patients with suspected upper airway lesions: A multicenter study

Objective

Narrow band imaging (NBI) improves diagnosis of laryngopharyngeal cancer, but most reported NBI studies are from experienced centers. Feasibility reports on use at everyday outpatient departments are needed.

Study Design

Researcher-initiated, prospective, multicenter.

Methods

Participating physicians were instructed in NBI technique during a 4-hour meeting. Patients underwent an examination that included endoscopy with white light (WL) high-definition (HD) TV and NBI filter in the selected time period. All suspicious lesions were biopsied. The medical records of patients with NBI negative findings were evaluated 6 months after the visit to detect all possible malignant lesions coming into view at mucosal sites. These were considered as false-negative cases, enabling long-term assess to the positive predictive value (NPV) of the protocol.

Results

We enrolled 125 patients. Of those, 84 (67.2%) were males and the median age was 65 years (range, 35–91). In analysis of the accuracy of WL HD TV and NBI against biopsy, the sensitivity and specificity of WL HD TV were 62% and 81%, respectively; and the sensitivity and specificity of NBI were 100% and 84%, respectively. The diagnostic accuracy of NBI was significantly better (P < 0.05). When analyzing medical records 6 months after the initial examination, we found three patients who had been diagnosed with a malignant lesion (NPV of NBI of 96.8%).

Conclusion

Narrow band imaging is readily implemented in an everyday outpatient practice, and there seems to be better detection rates of dysplastic/carcinoma lesions with HD NBI compared to HD WL.

Level of Evidence

2b. Laryngoscope, 2017

http://ift.tt/2kYjy6g

Efficiency of intraoperative neuromonitoring on voice outcomes after thyroid surgery

Voice disturbance is an important problem after thyroidectomy. The aim of this study was to evaluate the efficiency of intraoperative neuromonitoring (IONM) in reducing early phonation change by comparing postoperative voice outcomes.

http://ift.tt/2ltPZeW

Diagnosis and management of lentigo maligna: an observational study comparing 2005 with 2014 data in one institution

Summary

The incidence, clinical characteristics and management of lentigo maligna (LM) were assessed in a university hospital setting in 2005 and 2014. Multiple clinical variables were compared, and 28 and 43 cases, respectively were identified during the two time periods. The most common site of presentation was the cheek (50% vs. 44%), and an accurate clinical diagnosis of LM was made in 60% vs. 72%) of cases. Most of the patients received surgical treatment (75% in 2005 vs. 97% in 2014), with 47% and 33% of excisions, respectively, remaining involved at the peripheral surgical margin. During the 10-year follow-up for the 2005 cohort, 7 of the 28 patients had recurrence (3 of whom already had previously involved margins following surgery). This study shows that making an accurate clinical diagnosis of LM remains a significant challenge. Although surgery has become the preferred management option, achieving clear excision remains difficult, with involved margins increasing the risk of local recurrence and need for further intervention.

http://ift.tt/2kYf2Vm

Endoscopically assisted extracapsular dissection of pleomorphic adenoma of the parotid gland through a postauricular sulcus approach in young patients

We evaluated the aesthetic outcomes in 11 young patients (mean (range) age 21.7 (16–28) years) who had endoscopically assisted extracapsular dissection of benign pleomorphic adenomas of the parotid gland through a postauricular sulcus approach. The tumours varied in size from 1.5×1.0cm to 2.5×2.0cm, and all were removed completely without rupture. The cosmetic result was excellent in 10 patients and good in one. Patients were followed up for eight to 40 months, and there was no recurrence. The technique is simple and feasible, and it achieves excellent aesthetic results in young patients.

http://ift.tt/2lEzpuZ

Resolution of vocal fold leukoplakia during erlotinib treatment

Resolution of vocal fold leukoplakia during erlotinib treatment

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

6948891480

alsfakia@gmail.com

The most commonly prescribed ear drops : Tobradex (brand), Cipro HC (brand), Ciprodex (brand), Vosol (brand),acetic acid (Vosol–generic), VosolHC (brand),acetic acid/aluminum acetate (Domeboro–generic), Cortisporin (brand),neomycin, polymyxin B sulfates, and hydrocortisone (Cortisporin–generic), ofloxacin (generic), sulfacetamide (generic)

http://otorhinolarygology.blogspot.com/2017/02/the-most-commonly-prescribed-ear-drops.html

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

6948891480

alsfakia@gmail.com

Evaluation of ISO 4049: water sorption and water solubility of resin cements

The aim of this study was to evaluate the water sorption and solubility test design of ISO 4049 for resin cements. Sorption and solubility of six dual-curing resin cements [RelyX Unicem 2 Automix (RUN), Multilink Speed CEM (MLS), Panavia SA Plus (PSA), RelyX Ultimate (RUL), Multilink Automix (MLA), and Panavia V5 (PV5)] were analyzed by storage in distilled water after dual-curing. In addition, sorption and solubility during thermal cycling were assessed with self-cured and dual-cured specimens. After water storage, all cements revealed sorption in the range of 30 μg mm⁻³ except for PV5, for which sorption was markedly lower (mean ± SD = 20.8 ± 0.4 μg mm⁻³). Solubility values were negative for RUN and RUL (−2.1 ± 0.08 μg mm⁻³ and −1.9 ± 0.13 μg mm⁻³, respectively). All other cements attained positive values in the range of 0.4–0.8 μg mm⁻³. Thermal cycling effects were more pronounced. The assessment of water sorption according to ISO 4049 provides reliable results. Solubility results must be interpreted with care because absorbed water may distort the values.

http://ift.tt/2lm8e7w

American Thyroid Association Guidelines on the Management of Thyroid Nodules and Differentiated Thyroid Cancer Task Force Review and Recommendation on the Proposed Renaming of Encapsulated Follicular Variant Papillary Thyroid Carcinoma Without Invasion to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features

Thyroid , Vol. 0, No. 0.


http://ift.tt/2ltwtzh

Digitale Technologien für die Nasenchirurgie

Zusammenfassung

Die Fortschritte in der Computertechnik spiegeln sich auch in der Praxis der Rhinochirurgie wider und können neue Entwicklungen befördern. Ziel des Beitrages ist es, diesen Zusammenhang anhand verschiedener Innovationen zu verdeutlichen. Dazu werden die digitale Fotodokumentation bzw. Ergebnissimulation, die Anwendung interaktiver 3‑D-Modelle des Nasengerüstes und die numerische Simulation der Nasenströmung diskutiert.

http://ift.tt/2kXKljq

Forward Masking in Cochlear Implant Users: Electrophysiological and Psychophysical Data Using Pulse Train Maskers

Abstract

Electrical stimulation of auditory nerve fibers using cochlear implants (CI) shows psychophysical forward masking (pFM) up to several hundreds of milliseconds. By contrast, recovery of electrically evoked compound action potentials (eCAPs) from forward masking (eFM) was shown to be more rapid, with time constants no greater than a few milliseconds. These discrepancies suggested two main contributors to pFM: a rapid-recovery process due to refractory properties of the auditory nerve and a slow-recovery process arising from more central structures. In the present study, we investigate whether the use of different maskers between eCAP and psychophysical measures, specifically single-pulse versus pulse train maskers, may have been a source of confound.

In experiment 1, we measured eFM using the following: a single-pulse masker, a 300-ms low-rate pulse train masker (LTM, 250 pps), and a 300-ms high-rate pulse train masker (HTM, 5000 pps). The maskers were presented either at same physical current (Φ) or at same perceptual (Ψ) level corresponding to comfortable loudness. Responses to a single-pulse probe were measured for masker-probe intervals ranging from 1 to 512 ms. Recovery from masking was much slower for pulse trains than for the single-pulse masker. When presented at Φ level, HTM produced more and longer-lasting masking than LTM. However, results were inconsistent when LTM and HTM were compared at Ψ level. In experiment 2, masked detection thresholds of single-pulse probes were measured using the same pulse train masker conditions. In line with our eFM findings, masked thresholds for HTM were higher than those for LTM at Φ level. However, the opposite result was found when the pulse trains were presented at Ψ level.

Our results confirm the presence of slow-recovery phenomena at the level of the auditory nerve in CI users, as previously shown in animal studies. Inconsistencies between eFM and pFM results, despite using the same masking conditions, further underline the importance of comparing electrophysiological and psychophysical measures with identical stimulation paradigms.

http://ift.tt/2l5FUnf

Upregulation of thioredoxin-1 in activated human NK cells confers increased tolerance to oxidative stress

Abstract

Adoptive transfer of immune cells, such as T lymphocytes and NK cells, has potential to control cancer growth. However, this can be counteracted by immune escape mechanisms within the tumor microenvironment, including those mediated by reactive oxygen species (ROS). Here, we determined the levels of anti-oxidant molecules in NK cells and their capacity to overcome ROS-induced immune suppression. We investigated the effect of H₂O₂ on resting NK cells, IL-2-activated NK cells and NK cells expanded by coculture with the K562 leukemia cell line genetically modified to express membrane-bound IL-15 and 4-1BB ligand (K562-mb15-41BBL). Expression of anti-oxidant and anti-apoptotic genes was evaluated by expression array, and protein levels of anti-oxidant molecules by Western blot. Activated NK cells, IL-2-activated NK cells and NK cells expanded by K562-mb15-41BBL were significantly more resistant to H₂O₂-induced cell death than resting NK. Thioredoxin-1 (TXN1) and peroxiredoxin-1 (PRDX1) were also up-regulated in activated NK cells. Moreover, H₂O₂-induced cell death after IL-2 activation was significantly induced in the presence of an anti-TXN1-neutralising antibody. Collectively, these data document that activated NK cells can resist to H₂O₂-induced cell death by up-regulation of TXN1.

http://ift.tt/2ll60Fo

Mechanisms overseeing myeloid-derived suppressor cell production in neoplastic disease

Abstract

Perturbations in myeloid cell differentiation are common in neoplasia, culminating in immature populations known as myeloid-derived suppressor cells (MDSCs). MDSCs favor tumor progression due to their ability to suppress host immunity or promote invasion and metastasis. They are thought to originate from the bone marrow as a result of exposure to stromal- or circulating tumor-derived factors (TDFs). Although great interest has been placed on understanding how MDSCs function, less is known regarding how MDSCs develop at a transcriptional level. Our work explores the premise that MDSCs arise because cancer cells, through the production of certain TDFs, inhibit the expression of interferon regulatory factor-8 (IRF8) that is ordinarily essential for controlling fundamental properties of myeloid cell differentiation. Our interest in IRF8 has been based on the following rationale. First, it is well-recognized that IRF8 is a 'master regulator' of normal myelopoiesis, critical not only for producing monocytes, dendritic cells (DCs), and neutrophils, but also for controlling the balance of all three major myeloid cell types. This became quite evident in IRF8^−/− mice, whereby the loss of IRF8 leads to a disproportionate accumulation of neutrophils at the expense of monocytes and DCs. Second, we showed that such myeloid populations from IRF8^−/− mice exhibit similar characteristics to MDSCs from tumor-bearing mice. Third, in a reciprocal fashion, we showed that enforced expression of IRF8 in the myeloid system significantly mitigates tumor-induced MDSC accumulation and improves immunotherapy efficacy. Altogether, these observations support the hypothesis that IRF8 is an integral negative regulator of MDSC biology.

http://ift.tt/2ma8EMH

Tumor specific regulatory T cells in the bone marrow of breast cancer patients selectively upregulate the emigration receptor S1P1

Abstract

Regulatory T cells (Treg) hamper anti-tumor T-cell responses resulting in reduced survival and failure of cancer immunotherapy. Among lymphoid organs, the bone marrow (BM) is a major site of Treg residence and recirculation. However, the process governing the emigration of Treg from BM into the circulation remains elusive. We here show that breast cancer patients harbour reduced Treg frequencies in the BM as compared to healthy individuals or the blood. This was particularly the case for tumor antigen-specific Treg which were quantified by MHCII tumor peptide loaded tetramers. We further demonstrate that decreased Treg distribution in the BM correlated with increased Treg redistribution to tumor tissue, suggesting that TCR triggering induces a translocation of Treg from the BM into tumor tissue. Sphingosine-1-phosphate receptor 1 (S1P1)—which is known to mediate exit of immune cells from lymphoid organs was selectively expressed by tumor antigen-specific BM Treg. S1P1 expression could be induced in Treg by BM-resident antigen-presenting cells (BMAPCs) in conjunction with TCR stimulation, but not by TCR stimulation or BMAPCs alone and triggered the migration of Treg but not conventional T cells (Tcon) to its ligand Sphingosine-1-phosphate (S1P). Interestingly, we detected marked S1P gradients between PB and BM in breast cancer patients but not in healthy individuals. Taken together, our data suggest a role for S1P1 in mediating the selective mobilization of tumor specific Treg from the BM of breast cancer patients and their translocation into tumor tissue.

http://ift.tt/2ll3Plm

Editorial Board Page

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3





http://ift.tt/2kXW7dB

Pneumosinus Dilatans: Over 100 Years without an Etiology

Publication date: Available online 21 February 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Joseph A. Ricci
PurposePneumosinus dilatans (PD) is a rare pathologic hyperaeration of the paranasal sinuses, which causes significant deformation of the overlying bone and soft tissue. The condition occurs most commonly in the frontal sinus of young adult males who present with a variety of complaints, including cosmetic. Over 100 cases have been reported in the literature since it was first described in 1898; however, the etiology of this condition remains unclear.MethodsA systematic review of all available clinical publications on the subject of PD was conducted in the PubMed electronic database. The resultant articles were grouped based on evidence supporting or refuting various theoretical etiologies to further characterize the condition.ResultsA total of 134 known cases have been reported in 117 articles. Most affected patients are young males in the third decade of life. Only 19 (16.2%) articles offered some form of evidence in support of a particular etiology. The most substantiated etiologies of PD include: a "ball-valve" mechanism of sinus outflow obstruction that leads to air trapping or a primary fibro-osseous pathologic process that disrupts the cellular milieu. Less substantiated theories include: hormonal dysregulation or a spontaneously draining mucocele. No data exists to support causation by a gas forming bacteria. A bimodal distribution of incidence, a younger population (16 to 25) and an older population (36 to 40), may suggest multiple possible etiologies.ConclusionsSeveral theories on the etiology of PD exist, but none have been substantiated by reliable scientific evidence. We believe that standardizing the clinical evaluation, classification, management, and pathologic analysis of patients with PD may aid in elucidating its true etiology.



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Table of Contents

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3





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AAOMS Author Disclosure forms

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3





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The Trouble With Exact Change

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Thomas B. Dodson




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Journal of Oral and Maxillofacial Surgery

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3





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What a Shame: Increased Rates of OMS Resident Burnout May Be Related to the Frequency of Shamed Events During Training

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Michael C. Shapiro, Sowmya R. Rao, Jason Dean, Andrew R. Salama
PurposeShame is an ineffective tool in residency education that often results in depression, isolation, and worse patient care. This study aimed to assess burnout, depersonalization, and personal achievement levels in current oral and maxillofacial surgery (OMS) residents, to assess the prevalence of the use of shame in OMS residency training, and to determine whether there is a relation between shame exposure and resident burnout, depersonalization, and personal achievement levels.Materials and MethodsAn anonymous 20-question cross-sectional survey was developed incorporating the Maslach Burnout Index and a previously validated shame questionnaire and sent to all OMS program directors affiliated with the American Association of Oral and Maxillofacial Surgeons for distribution among their respective residents in 2016. Univariate analyses were used to determine the distribution of the predictor (shame) and outcome (burnout) by gender and by frequency of shaming events. Multivariable logistic regression analysis was used to assess the relation of shame to burnout. A 2-sided P value less than .05 was considered statistically significant.ResultsTwo hundred seventeen responses were received; 82% of respondents were men (n = 178), 95% were 25 to 34 years old (n = 206), and 58% (n = 126) were enrolled in a 4-year program. Frequently shamed residents were more likely to have depression (58 vs 22%; P < .0001), isolation (55 vs 22%; P < .0001), and poor job performance (50 vs 30%; P < .0001). Residents who were frequently shamed were more likely to experience moderate to severe burnout (odds ratio = 4.6; 95% confidence interval, 2.1-10.0; P < .001) and severe depersonalization (odds ratio = 5.1; 95% confidence interval, 2.1-12.0; P < .0001) than residents who had never or infrequently been shamed.ConclusionThere is a clear relation between the number of shame events and burnout and depersonalization levels. It is important to understand the negative impact that the experience of shame has on residents, including its unintended consequences.



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What Is the Role of Elective Neck Dissection in the Treatment of Patients With Buccal Squamous Cell Carcinoma and Clinically Negative Neck Findings?

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Jasjit K. Dillon, Akashdeep Villing, Scott Jones, Neal Futran, Hans Brockhoff, Brent Ward
PurposeBuccal squamous cell carcinoma (BSCC) is rare in the United States. Given its location, few anatomic barriers to its spread exist, and it has been found to have a high locoregional recurrence rate. The role of elective neck dissection (END) in the clinically negative neck (N0) is not clear. In the present study, we measured the effect of END on the locoregional and distant metastasis rates among patients with clinically N0 BSCC.Materials and MethodsA retrospective cohort study was conducted. The sample included subjects diagnosed with BSCC. The primary predictor variable was END status (yes vs no). The primary outcome variable was locoregional recurrence. The secondary outcome variables were distant metastasis and the 2- and 5-year survival rates. Other variables collected included demographic data, initial operation, adjuvant therapy, pathologic data, and stage. Kaplan-Meier and Cox proportional hazards statistics were computed.ResultsThe sample included 20 subjects with clinical N0 BSCC and a mean age of 67 years (range 42-88); 55% were men. The disease stage was T1 in 30%, T2 in 40%, T3 in 15%, and T4 in 15%. Fifteen subjects underwent END. Of the 5 who had not undergone END, all 5 (100%) had locoregional recurrence and 1 (20%) had metastasis. Of the 15 who had undergone END, 5 (33%) had locoregional recurrence and 1 (7%) had metastasis (P = .002). The 2- and 5-year survival rates for N0 patients without END was 80% and 40%, respectively, compared with 93% and 87% for those who had undergone END.ConclusionsEND had a therapeutic role, resulting in a lower locoregional recurrence rate. Also, the 2- and 5-year survival rates were greater for those who had undergone END.



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Societal Preference for Gender of Surgeons Performing Patients' Surgery

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Alyssa Franklin, Caroline K. Carrico, Daniel M. Laskin
PurposePrevious studies have shown that there may be a bias among some male oral and maxillofacial surgeons regarding women practicing in the specialty. The purpose of this study was to determine if there is a similar bias in the general public.Patients and MethodsWe performed a survey of 65 patients of various genders, educational levels, and ages asking them their surgeon gender preference for extraction of a tooth, removal of impacted third molars, and cosmetic surgery, as well as the reasons for their preference.ResultsOf respondents, 91% had no preference regarding surgeon gender for tooth extraction, 88% for removal of impacted teeth, and 83% for cosmetic surgery. There was no difference in gender preference based on the respondents' gender, educational level, or age.ConclusionsThere does not appear to be a gender bias against female oral and maxillofacial surgeons in the general population.



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Phosphorylated Epidermal Growth Factor Receptor Expression Is Associated With Clinicopathologic Parameters and Patient Survival in Mobile Tongue Squamous Cell Carcinoma

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Stamatios Theocharis, Constantinos Giaginis, Eugene Dana, Irene Thymara, Jose Rodriguez, Efstratios Patsouris, Jerzy Klijanienko
PurposePhosphorylated epidermal growth factor receptor (pEGFR) activates several signaling pathways, resulting in tumor-promoting cellular activities, and has been implicated in malignant transformation and disease progression. The present study evaluated the clinical significance of pEGFR protein expression in mobile tongue squamous cell carcinoma (SCC).Materials and MethodsThe present cohort study included 48 patients with mobile tongue SCC. We evaluated whether pEGFR immunohistochemical protein expression is associated with clinical variables and patient outcome.ResultsOf the 48 patients included in the present cohort study, 25 were men and 23 were women. The median patient age was 60 years (interquartile range 53 to 72). pEGFR protein expression was significantly increased in well-differentiated tumors compared with poorly differentiated tumors (P = .001). Elevated pEGFR protein expression was significantly more frequently observed in mobile tongue SCC cases with a well-defined tumor shape and an earlier disease stage (P = .010 and P = .019, respectively). Patients with mobile tongue SCC presenting with elevated pEGFR expression had longer overall and disease-free survival times compared with those with low pEGFR expression (P = .015 and P = .006, respectively; log-rank test). On multivariate analysis, pEGFR expression proved to be an independent prognostic factor of both overall and disease-free survival (P = .008 and P = .044, respectively; Cox regression analysis).ConclusionsThe results of the present study support evidence that the pEGFR signaling pathway might be implicated in the malignant transformation of mobile tongue SCC. Additional studies are recommended to validate whether pEGFR could be used as a potential biomarker and therapeutic target in mobile tongue SCC.



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Socket Grafting

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Michael S. Block




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Safety Concepts in the Anesthetic Management of Patients

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Jeffrey D. Bennett




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Does Restriction of Public Health Care Dental Benefits Affect the Volume, Severity, or Cost of Dental-Related Hospital Visits?

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): David Salomon, R. Eric Heidel, Antonia Kolokythas, Michael Miloro, Thomas Schlieve
PurposeOn July 1, 2012, the Illinois legislature passed the Save Medicaid Access and Resources Together (SMART) Act, which restricts adult public dental insurance coverage to emergency-only treatment. The purpose of this study was to measure the effect of this restriction on the volume, severity, and treatment costs of odontogenic infections in an urban hospital.Materials and MethodsA retrospective cohort study of patients presenting for odontogenic pain or infection at the University of Illinois Hospital was performed. Data were collected using related International Classification of Diseases, Ninth Revision codes from January 1, 2011 through December 31, 2013 and divided into 2 cohorts over consecutive 18-month periods. Outcome variables included age, gender, insurance status, oral and maxillofacial surgery (OMS) consultation, imaging, treatment, treatment location, number of hospital admission days, and inpatient care level. Severity was determined by the presence of OMS consultation, incision and drainage, hospital admission, and cost per encounter. Hospital charges were used to compare the cost of care between cohorts. Between-patients statistics were used to compare risk factors and outcomes between cohorts.ResultsOf 5,192 encounters identified, 1,405 met the inclusion criteria. There were no significant differences between cohorts for age (P = .28) or gender (P = .43). After passage of the SMART Act, emergency department visits increased 48%, surgical intervention increased 100%, and hospital admission days increased 128%. Patients were more likely to have an OMS consult (odds ratio [OR] = 1.42; 95% confidence interval [CI], 1.11-1.81), an incision and drainage (OR = 1.48; 95% CI, 1.13-1.94), and a longer hospital admission (P = .04). The average cost per encounter increased by 20% and the total cost of care increased by $1.6 million.ConclusionAfter limitation of dental benefits, there was an increase in the volume and severity of odontogenic infections. In addition, there was an escalated health care cost. The negative public health effects and increased economic impact of eliminating basic dental care show the importance of affordable and accessible preventative oral health care.



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Surgical Management of Progressive Hemifacial Atrophy With De-Epithelialized Profunda Artery Perforator Flap: A Case Report

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Zoltán Lóderer, Ágnes Janovszky, Péter Lázár, József Piffkó
Progressive hemifacial atrophy (PHA) is a rare disorder characterized by slow, unilateral atrophy of the soft tissues and bones of the craniofacial region. The defect becomes more pronounced with age, leading to esthetic and functional deficits. However, the proper timing and method of surgical reconstruction are still debated. The correction of this defect markedly influencing the quality of life of the patient can be achieved with less invasive to more invasive surgical approaches. A 21-year-old female patient with hemifacial atrophy and extensive alopecia presented to our clinic. Considering the body type and the expectations of the patient, a profunda artery perforator flap was applied for the reconstruction and esthetic improvement of the facial region. The facial asymmetry attenuated after the reconvalescence period. This case shows that in the up-to-date surgical treatment of severe PHA, the use of microvascular free flaps may provide a better approach when trying to achieve an acceptable esthetic result. This is the first time that a profunda artery perforator flap was used to restore facial asymmetry caused by PHA.



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Prevention of Oral Candidiasis After Free Flap Surgery: Role of 3% Sodium Bicarbonate Saline in Oral Care

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Yue Yang, Fang Zhang, Xin Lyu, Zhimin Yan, Hong Hua, Xin Peng
PurposeRelevant reports about oral candidiasis status and prevention measures after free flap surgery for the oral and maxillofacial region are limited. The present study explored oral candidiasis status after free flap surgery and its prevention through a prospective comparative study.Patients and MethodsOne hundred four patients were randomized to a control group (n = 54) and an experimental group (n = 50). Compared with the control group, the experimental group was provided an additional 3% sodium bicarbonate saline solution for oral care after free flap surgery. The incidence of oral candidiasis was evaluated by objective examination (saliva culture and salivary pH measurement) and subjective evaluation (clinical signs of oral candidiasis) at admission and from postoperative days 1 to 14.ResultsThe salivary pH values of the 2 groups were lower than the normal salivary pH, and postoperative salivary pH values were always lower than the active range of oral lysozymes in the control group. The salivary pH values of the experimental group were higher than those of the control group from postoperative days 6 to 14 (P < .05). The incidence of oral candidiasis was 13.0% in the control group, which was higher than that in the experimental group (2.0%; P < .05). In addition, advanced age, use of a free flap for the simultaneous repair of intraoral and paraoral defects, and a combination of 2 antibiotic types were risk factors for oral candidiasis.ConclusionOral candidiasis was common in patients after free flap reconstruction surgery, and the use of 3% sodium bicarbonate saline solution for oral care effectively prevented it.



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p16 Immunohistochemistry Is a Useful Diagnostic Adjunct in Cases of Metastatic Cervical Carcinoma of Unknown Origin

Publication date: March 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 3
Author(s): Marc R. Rohrbach, Christopher J. Britt, Michael Schwalbe, Aaron M. Wieland, Gregory K. Hartig
PurposeMetastatic cervical carcinoma of unknown primary (MCCUP) is increasing in frequency owing in part to rising human papillomavirus (HPV)-driven oropharyngeal carcinoma. Identifying the primary site is valuable, because it is associated with increased survival and decreased morbidity. HPV-positive cervical nodal disease focuses attention on the oropharynx for directed biopsy examinations, including tonsillectomy. When the primary is small, carcinoma might not be apparent by traditional hematoxylin and eosin (H&E) staining alone.Materials and MethodsThis report describes 2 cases of p16-positive MCCUP in which a small primary carcinoma was not readily identified in surgical specimens using H&E staining.ResultsAdditional evaluation of the specimens with p16 immunohistochemistry (IHC) showed carcinoma in these 2 cases.ConclusionsWhen H&E staining does not show carcinoma in cases of MCCUP, p16 IHC should be considered given the high prevalence of HPV-positive MCCUP and the potential for identification of a small primary tumor that might otherwise be missed with H&E staining.



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Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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Response to inhaled corticosteroids on serum CD28, quality of life, and peak expiratory flow rate in bronchial asthma

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Erratum

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Erratum

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Erratum

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Can the burden of disease due to food allergy be prevented?

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The emotional, social, and financial burden of food allergies on children and their families

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The National Institutes of Allergy and Infectious Diseases sponsored guidelines on preventing peanut allergy: A new paradigm in food allergy prevention

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Understanding alpha-1 antitrypsin deficiency: A review with an allergist's outlook

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State-of-the-art testing for alpha-1 antitrypsin deficiency

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Allergen immunotherapy at university health services and allergist's reasons for guidelines nonadherence

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American Academy of Asthma, Allergy & Immunology membership experience with venom immunotherapy in chronic medical conditions and pregnancy, and in young children

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Relation of indoor and outdoor airborne fungal spore levels in the Kansas City metropolitan area

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The persistence of chronic spontaneous urticaria in childhood is associated with the urticaria activity score

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Health-related quality of life with hereditary angioedema following prophylaxis with subcutaneous C1-inhibitor with recombinant hyaluronidase

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What accounts for the association between late preterm births and risk of asthma?

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A randomized study of BI 671800, a CRTH2 antagonist, as add-on therapy in poorly controlled asthma

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For the Patient

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Medical and Surgical Advancements in the Management of Cystic Fibrosis Chronic Rhinosinusitis

Abstract

Purpose of Review

The purpose of this review is to provide otolaryngologists with the most up-to-date advancements in both the medical and surgical management of CF-related sinus disease.

Recent Findings

Recent studies have supported more aggressive chronic rhinosinusitis (CRS) management, often with a combination of both medical and surgical therapies. Comprehensive treatment strategies have been shown to reduce hospital admissions secondary to pulmonary exacerbations in addition to improving CRS symptoms. Still, current management strategies are lacking in both high-level evidence and standardized guidelines.

Summary

The unified airway model describes the bi-directional relationship between the upper and lower airways as a single functional unit and suggests that CRS may play a pivotal role in both the development and progression of lower airway disease. Current strategies for CF CRS focus primarily on amelioration of symptoms with antibiotics, nasal saline and/or topical medicated irrigations, and surgery. However, there are no definitive management guidelines and there remains a persistent need for additional studies. Nevertheless, otolaryngologists have a significant role in the overall management of CF, which requires a multidisciplinary approach and a combination of both surgical and medical interventions for optimal outcomes of airway disease. Here, we present a review of currently available literature and summarize medical and surgical therapies best suited for the management of CF-related sinus disease.

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Preliminary evidence of improved cognitive performance following vestibular rehabilitation in children with combined ADHD (cADHD) and concurrent vestibular impairment

Publication date: Available online 21 February 2017
Source:Auris Nasus Larynx
Author(s): Younes Lotfi, Nima Rezazadeh, Abdollah Moossavi, Hojjat Allah Haghgoo, Reza Rostami, Enayatollah Bakhshi, Faride Badfar, Sedigheh Farokhi Moghadam, Vahid Sadeghi-Firoozabadi, Yousef Khodabandelou
ObjectiveBalance function has been reported to be worse in ADHD children than in their normal peers. The present study hypothesized that an improvement in balance could result in better cognitive performance in children with ADHD and concurrent vestibular impairment. This study was designed to evaluate the effects of comprehensive vestibular rehabilitation therapy on the cognitive performance of children with combined ADHD and concurrent vestibular impairment.MethodsSubject were 54 children with combined ADHD. Those with severe vestibular impairment (n=33) were randomly assigned to two groups that were matched for age. A rehabilitation program comprising overall balance and gate, postural stability, and eye movement exercises was assigned to the intervention group. Subjects in the control group received no intervention for the same time period. Intervention was administered twice weekly for 12 weeks. Choice reaction time (CRT) and spatial working memory (SWM) subtypes of the Cambridge Neuropsychological Test Automated Battery (CANTAB) were completed pre- and post-intervention to determine the effects of vestibular rehabilitation on the cognitive performance of the subjects with ADHD and concurrent vestibular impairment. ANCOVA was used to compare the test results of the intervention and control group post-test.ResultsThe percentage of correct trial scores for the CRT achieved by the intervention group post-test increased significantly compared to those of the control group (p=0.029). The CRT mean latency scores were significantly prolonged in the intervention group following intervention (p=0.007) compared to the control group. No significant change was found in spatial functioning of the subjects with ADHD following 12 weeks of intervention (p>0.05).ConclusionThe study highlights the effect of vestibular rehabilitation on the cognitive performance of children with combined ADHD and concurrent vestibular disorder. The findings indicate that attention can be affected by early vestibular rehabilitation, which is a basic program for improving memory function in such children. Appropriate vestibular rehabilitation programs based on the type of vestibular impairment of children can improve their cognitive ability to some extent in children with ADHD and concurrent vestibular impairment (p>0.05).



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Quantitative representation of Eustachian tube component movements during swallowing

Publication date: Available online 21 February 2017
Source:Auris Nasus Larynx
Author(s): Selma Cetin, Miriam S. Teixeira, Cuneyt M. Alper
ObjectiveDescribes a method of dynamic video-endoscopy of the Eustachian tube (ET) orifice at the nasopharynx to quantitatively represent ET component movements during swallowing using a graphic function and analyze their importance to its opening mechanics.MethodsThis was a pilot study of relational event capture using a polar coordinate system applied to trans-nasal video-endoscopic recordings of the ET during 3 swallows in 5 adults. After topical anesthesia of the nose, a 45° telescope was introduced unilaterally and focused on the ipsilateral ET orifice. For each recording, consecutive still-frame images were analyzed by identifying 4 fixed-point locators; the luminal apex, lateral and medial walls and the torus. A frame-normal, horizontal line was constructed through the apex and, then, the medial angles defined at the intersection of the horizontal line and the lines from apex to each point locator were measured. The magnitudes of these angles were plotted as a function of time (i.e. successive frames) for each swallow.ResultsThe resulting graphs captured the "in plane" relational movements for the locator points during a swallow. Complex interactions among the ET components were resolvable and the patterns were reproducible across swallows. Individual peculiarities observable on review of the corresponding "movies" such as double-swallows, delayed swallows and ET luminal constriction were easily identified in the graphic representation.ConclusionThis methodology is potentially useful for summary presentations of the ET mechanics of individual patients and for quantifying differences in those mechanics between groups defined by their history of middle-ear disease.



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Efficiency of intraoperative neuromonitoring on voice outcomes after thyroid surgery

Publication date: Available online 21 February 2017
Source:Auris Nasus Larynx
Author(s): Seung-Kuk Baek, Kijeong Lee, Dongju Oh, Sung Hoon Kang, Soon-Young Kwon, Jeong-Soo Woo, Jae-Gu Cho, Kyung Ho Oh, Doh Young Lee, Kwang-Yoon Jung
ObjectiveVoice disturbance is an important problem after thyroidectomy. The aim of this study was to evaluate the efficiency of intraoperative neuromonitoring (IONM) in reducing early phonation change by comparing postoperative voice outcomes.MethodsThe study retrospectively enrolled 68 consecutive female patients who had undergone IONM thyroidectomy for papillary thyroid carcinoma occurring between January 2014 and November 2014. A historical group of 117 similar female patients not receiving IONM thyroidectomy was used as an external control. Voice analyses were performed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Voice outcomes between the IONM group and no IONM group were compared in patients who underwent hemithyroidectomy and total thyroidectomy.ResultsIn patients who underwent IONM, there were significantly smaller changes in the fundamental frequency at postoperative 1 month and in the maximum voice pitch of the voice range profile at postoperative 1 week irrespective of the extent of thyroid surgery.ConclusionIONM during thyroid surgery resulted in better outcomes regarding fundamental frequency and high-pitch voice in the early postoperative period. IONM appears to be an effective method to reduce temporary phonation alteration after thyroid surgery.



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Polyglycolic acid sheet attached with fibrin glue can facilitate faster epithelialization of the mastoid cavity after canal wall-down tympanoplasty

Publication date: Available online 20 February 2017
Source:Auris Nasus Larynx
Author(s): Taisuke Kobayashi, Kiyofumi Gyo, Masahiro Komori, Masamitsu Hyodo
ObjectiveThis study retrospectively investigated whether polyglycolic acid (PGA) sheet attached to the bone surface using fibrin glue facilitate faster epithelialization of the mastoid bowl after canal wall-down (CWD) tympanoplasty compared to a simple dressing using poly-N-acetyl-glucosamine (Kichin) sheet.Materials and MethodsAfter completion of the CWD tympanoplasty, PGA sheet (n=16, PGA group) with fibrin glue or Kichin sheet (n=38, Kichin group) were placed on the bone surface of the mastoid bowl.ResultsPostoperative epithelialization of the mastoid cavity was significantly (p<0.05) faster in the PGA group than in the Kichin group (mean 135 versus 244 days, respectively). Use of the Kaplan–Meier method showed that only the short-term epithelialization rate (up to 100 days after operation) was significantly higher. No major adverse effects related to either procedure were seen.ConclusionEpithelialization of the mastoid bowl after CWD tympanoplasty was faster in the postoperative short term when it was dressed with PGA sheet using fibrin glue compared with Kichin sheet.



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Folgen kritischer Erkrankung und mögliche Interventionen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 137-144
DOI: 10.1055/s-0042-103263

Nach überlebter kritischer Erkrankung leiden Patienten häufig unter einer persistierenden körperlichen und mentalen Morbidität, die nicht allein auf die Grunderkrankungen zurückzuführen ist. Eine häufig zu findende Kombination aus physischen, psychischen und kognitiven Defiziten wird als Post-intensive Care Syndrome (PICS) bezeichnet. Der nachfolgende Artikel beleuchtet die Epidemiologie dieser Beeinträchtigungen und stellt post-intensivmedizinische Interventionen mit dem Ziel der Prävention und Therapie vor.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Ecstasy-Intoxikation mit disseminierter intravasaler Gerinnung und Multiorganversagen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 145-151
DOI: 10.1055/s-0042-118022

Der vorliegende Fall beschreibt die frühklinische Versorgung eines Patienten mit schwerer Methyl-endioxymetamphetamin-Intoxikation (Ecstasy). Es wird die Historie stimulierender psychotroper Substanzen und die Wirkweise moderner Psychostimulanzien dargestellt. Daten aus dem österreichischen Drogenbericht zeigen die Verlagerung des Konsums „harter Drogen" wie z. B. Opioiden hin zu Cannabis und Amphetaminderivaten. Der letale Verlauf im beschriebenen Fall zeigt das hohe Gefahrenpotenzial derartiger Substanzen und weist auf die Notwendigkeit rechtzeitiger, aggressiver intensivmedizinischer Therapie hin.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Telemedizin: „TEMPiS“-Netzwerk für Schlaganfallbehandlung in der Regelversorgung

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 127-136
DOI: 10.1055/s-0042-108417

Die Versorgung von über 250 000 Schlaganfallpatienten jährlich allein in Deutschland stellt die Gesundheitssysteme vor große Herausforderungen. Mit der Gründung von Stroke Units, der Etablierung standardisierter Abläufe in Diagnostik und Therapie, der Einführung neuer Therapieverfahren wie Thrombolyse und Thrombektomie konnte die Schlaganfalltherapie hierzulande in den letzten Jahrzehnten bereits deutlich verbessert werden. Die Gründung telemedizinischer Schlaganfall-Netzwerke war hierbei ein Durchbruch in der Versorgung von Patienten im ländlichen Raum. TEMPiS war eines der ersten Netzwerke und ist, bezogen auf die Zahl versorgter Patienten und durchgeführter Thrombolysen, eines der weltweit führenden telemedizinischen Schlaganfall-Netzwerke. Nach einer positiven Outcome-Studie wurde es 2006 von den Bayerischen Krankenkassen in die Regelversorgung überführt. Neben dem Telekonsildienst haben im TEMPiS-Netzwerk die Qualitätssicherung, regelmäßige Fortbildungen für alle Therapeutengruppen, der Einsatz standardisierter Abläufe und die Gründung von Stroke Units bzw. Tele-Stroke-Units zu einer verbesserten Versorgung der Schlaganfallpatienten in den TEMPiS-Kliniken geführt. Die wissenschaftlichen Ergebnisse aus dem Netzwerk haben dabei der telemedizinischen Schlaganfallbehandlung weltweit zu Bedeutung verholfen und Wege aufgezeigt, wie die Versorgungslücke für viele Patienten im ländlichen Raum geschlossen werden könnte.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Telemedizin: Chancen in der Schmerztherapie

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 118-126
DOI: 10.1055/s-0042-108714

Die Telemedizin hat besonders in der Schmerztherapie großes Potenzial, die Versorgung der Patienten zu verbessern. Sie bietet die Chance, therapeutische Beratung und Behandlung über die Grenzen spezialisierter Schmerzzentren hinweg auszuweiten. Der folgende Beitrag beleuchtet die Gründe für den Einsatz der Telemedizin in der Schmerztherapie, stellt verschiedene Modelle vor und geht auf wirtschaftliche Aspekte ein.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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http://ift.tt/2llqfmk

Telemedizin: Potenziale in der Notfallmedizin

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 107-117
DOI: 10.1055/s-0042-108713

Die telemedizinische Vernetzung zwischen medizinischem Personal und Spezialisten hat sich in der prähospitalen Notfallmedizin – wie auch in anderen medizinischen Bereichen – als vorteilhaft erwiesen. In der Notfallmedizin haben sich telemedizinische Teilkomponenten entwickelt, die für jeweils einzelne Krankheitsbilder anwendbar sind. Neu hingegen ist ein System, das ein breites notfallmedizinisches Spektrum als ergänzendes Strukturelement des existierenden boden- und luftgebundenen Rettungssystems abdecken kann. Es wird dargestellt, warum Telemedizin in der Notfallmedizin notwendig und sinnvoll ist, und die wichtigsten Strukturmerkmale werden erläutert. Ein aus unterschiedlichen Hard- und Softwarekomponenten bestehendes System (Telenotarzt-Arbeitsplatz, Server-Infrastruktur, mobile und im Rettungswagen fest verbaute Übertragungseinheit) gewährleistet die Verfügbarkeit medizinischer Daten und den sicheren Datentransfer (Sprache, Echtzeit-Vitalparameter-Kurven und Werte, Fotos, Videostream, 12-Kanal-EKG etc.) in Echtzeit. Basis für eine sichere Telemedizin sind die Strukturempfehlungen der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin. Anwendbar ist die Telemedizin bei unterschiedlichsten Krankheitsbildern und Indikationen. Jedoch unterliegt das System auch Grenzen und Limitationen. Schlussfolgerungen Telemedizin in der prähospitalen Phase ist sicher, erreicht im Vergleich zum konventionellen Notarztsystem eine bessere Dokumentationsqualität, verkürzt die ärztliche Bindungszeit um 50 %, reduziert die Gesamtzahl der ärztlich begleiteten Rettungsdiensteinsätze und zeigt eine mindestens gleichwertige medizinische Versorgungsqualität.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Erratum: Pssst … AINS-Secrets: Heute aus der Gynäkologie

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 84-84
DOI: 10.1055/s-0043-101363

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Telemedizin: Chancen und Grenzen in der Intensivmedizin

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 94-106
DOI: 10.1055/s-0042-108712

Tele-Intensivmedizin ist eine Möglichkeit, das Behandlungsergebnis, gemessen an der Sterblichkeit, Behandlungsdauer sowie Morbidität, zu verbessern. Sie ermöglicht wohnortnahe intensivmedizinische Versorgung und die Möglichkeit des Daten- und Informationsaustauschs mit spezialisierten Zentren in Echtzeit. Im Folgenden stellen wir die unterschiedlichen Realisierungsmöglichkeiten und ihre Effekte sowie die Grenzen der Tele-Intensivmedizin dar.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

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Status quo und Potenzial der Telemedizin in Deutschland

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 90-93
DOI: 10.1055/s-0042-108711

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Rare anatomical variant of the cervical internal carotid artery

Publication date: Available online 20 February 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): G. Agrawal, A. Gupta, V. Chaudhary, H. Mazhar, S. Tiwari
Neck dissection is routine for the management of cancers of the head and neck. Knowledge of anatomical variants in the carotid artery system at various levels of dissection should prevent inadvertent injury to major blood vessels, which can cause massive bleeding. We report a rare 180° sharp bend in the cervical course of the internal carotid artery at level II, which we found during a modified neck dissection.



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Head and neck surgery: tracheostomy or not?

Publication date: Available online 20 February 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): R. Lewis, N. Scott, M. Fardy




http://ift.tt/2mahKZE

Photographic technique for the quantitative assessment of lagophthalmos and eyelid position in patients with facial palsy

Publication date: Available online 21 February 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): M. Zago, F. Tarabbia, L. Bassetti, F. Biglioli, C. Sforza




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Galactose-α-1,3-Galactose: Atypical Food Allergen or Model IgE Hypersensitivity?

Abstract

Purpose of Review

Galactose-α-1,3-galactose (α-gal) is a carbohydrate allergen with several unique characteristics. In this article, we discuss some recent advances in our understanding of the 'alpha-gal syndrome,' highlight data supporting the role of ticks in pathogenesis, and speculate on immune mechanisms that lead to sensitization.

Recent Findings

First described as the target of IgE in individuals suffering immediate hypersensitivity reactions to the novel anti-EGF monoclonal antibody cetuximab, it is now clear that α-gal sensitization is associated with mammalian meat allergy as well as reactions to other mammalian products. Unlike traditional IgE-mediated food allergies, reactions to α-gal often do not manifest until several hours following an exposure, although co-factors can influence the presentation. Multiple pieces of evidence, including recent work with a mouse model, point to the fact that sensitization is mediated by exposure to certain hard ticks and increasingly we are aware of its globally widespread impact.

Summary

The oligosaccharide α-gal represents a novel allergen with several unusual clinical features. It has been recognized now on multiple continents and its clinical presentation can be quite variable. Moreover, efforts to delineate the mechanisms leading to α-gal sensitization may have ramifications for our broader understanding of type 2 immunity.

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Speech audiometric assessment of informational masking

Abstract

Background

In communication situations with multiple speakers, speech recognition is adversely affected by energetic masking (EM) and informational masking (IM). IM characterizes masking effects caused by irrelevant information from competing speakers. This work investigates an approach to assess IM based on the Oldenburg Sentence Test (OLSA). Furthermore, the influence of interaural time differences (ITD) and aging effects on IM are considered.

Materials and methods

IM was measured by superimposing two sentences from the OLSA. The beginning of the target sentence was indicated by the keyword "Stefan". To segregate between target and masker sentences, ITDs from 50 to 400 μs were included. The participants were asked to selectively attend to the target sentence and repeat the spoken words. Potential factors associated with speech recognition results were assessed by an auditory measure of temporal fine structure and a neuropsychological profile. The study comprised 16 normal-hearing listeners between 18 and 77 years of age.

Results

Despite the clinically normal hearing participants, the analysis showed a significant relationship between speech recognition outcome and pure tone thresholds. All participants benefited from small ITDs between the target and masker sentence with regard to the unmasking of IM. The magnitude of unmasking could not be explained by any of the factors assessed in this study. Error analysis and the comparison with the literature reveal that the OLSA could be a useful tool to assess IM. Also in line with the current literature is the relationship between speech recognition outcome and pure tone thresholds, as well as the strong effect of ITDs on the release from IM.

Conclusion

Speech audiometric assessment of IM is of high relevance with regard to everyday communication situations. Due to its structure, the OLSA seems to be a useful tool for determining IM.

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An Interactive Macrophage Signal Transduction Map Facilitates Comparative Analyses of High-Throughput Data [SYSTEMS IMMUNOLOGY]

Macrophages (Ms) are key players in the coordination of the lifesaving or detrimental immune response against infections. The mechanistic understanding of the functional modulation of Ms by pathogens and pharmaceutical interventions at the signal transduction level is still far from complete. The complexity of pathways and their cross-talk benefits from holistic computational approaches. In the present study, we reconstructed a comprehensive, validated, and annotated map of signal transduction pathways in inflammatory Ms based on the current literature. In a second step, we selectively expanded this curated map with database knowledge. We provide both versions to the scientific community via a Web platform that is designed to facilitate exploration and analysis of high-throughput data. The platform comes preloaded with logarithmic fold changes from 44 data sets on M stimulation. We exploited three of these data sets—human primary Ms infected with the common lung pathogens Streptococcus pneumoniae, Legionella pneumophila, or Mycobacterium tuberculosis—in a case study to show how our map can be customized with expression data to pinpoint regulated subnetworks and druggable molecules. From the three infection scenarios, we extracted a regulatory core of 41 factors, including TNF, CCL5, CXCL10, IL-18, and IL-12 p40, and identified 140 drugs targeting 16 of them. Our approach promotes a comprehensive systems biology strategy for the exploitation of high-throughput data in the context of M signal transduction. In conclusion, we provide a set of tools to help scientists unravel details of M signaling. The interactive version of our M signal transduction map is accessible online at http://ift.tt/2jVWjfP.

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Th22 Cells Form a Distinct Th Lineage from Th17 Cells In Vitro with Unique Transcriptional Properties and Tbet-Dependent Th1 Plasticity [MUCOSAL IMMUNOLOGY]

Th22 cells are a major source of IL-22 and have been found at sites of infection and in a range of inflammatory diseases. However, their molecular characteristics and functional roles remain largely unknown because of our inability to generate and isolate pure populations. We developed a novel Th22 differentiation assay and generated dual IL-22/IL-17A reporter mice to isolate and compare pure populations of cultured Th22 and Th17 cells. Il17a fate-mapping and transcriptional profiling provide evidence that these Th22 cells have never expressed IL-17A, suggesting that they are potentially a distinct cell lineage from Th17 cells under in vitro culture conditions. Interestingly, Th22 cells also expressed granzymes, IL-13, and increased levels of Tbet. Using transcription factor–deficient cells, we demonstrate that RORt and Tbet act as positive and negative regulators of Th22 differentiation, respectively. Furthermore, under Th1 culture conditions in vitro, as well as in an IFN-–rich inflammatory environment in vivo, Th22 cells displayed marked plasticity toward IFN- production. Th22 cells also displayed plasticity under Th2 conditions in vitro by upregulating IL-13 expression. Our work has identified conditions to generate and characterize Th22 cells in vitro. Further, it provides evidence that Th22 cells develop independently of the Th17 lineage, while demonstrating plasticity toward both Th1- and Th2-type cells.

http://ift.tt/2ll8kw6

A Database of Human Immune Receptor Alleles Recovered from Population Sequencing Data [NOVEL IMMUNOLOGICAL METHODS]

High-throughput sequencing data from TCRs and Igs can provide valuable insights into the adaptive immune response, but bioinformatics pipelines for analysis of these data are constrained by the availability of accurate and comprehensive repositories of TCR and Ig alleles. We have created an analytical pipeline to recover immune receptor alleles from genome sequencing data. Applying this pipeline to data from the 1000 Genomes Project we have created Lym1K, a collection of immune receptor alleles that combines known, well-supported alleles with novel alleles found in the 1000 Genomes Project data. We show that Lym1K leads to a significant improvement in the alignment of short read sequences from immune receptors and that the addition of novel alleles discovered from genome sequence data are likely to be particularly significant for comprehensive analysis of populations that are not currently well represented in existing repositories of immune alleles.

http://ift.tt/2l5zy7A

Etv5 Regulates IL-10 Production in Th Cells [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

IL-10 is an immunoregulatory cytokine that has broad effects across the immune system. In Th cell subsets, Th2 cells produce considerable amounts of IL-10. The transcription factors that regulate IL-10 production in Th2 cells are still incompletely described. In this study, we demonstrate that the ETS family transcription factor ETS variant (Etv)5 regulates IL-10 production in Th2 cells. T cell–specific Etv5-deficient and littermate control mice demonstrated that IL-10 production and gene expression were significantly decreased in the absence of Etv5. In an Aspergillus fumigatus extract–induced inflammation model, IL-10–producing CD4⁺ T cells in bronchoalveolar lavage and lung were significantly decreased in mice that lacked Etv5 in T cells, compared with control mice. We showed that Etv5 directly binds to the Il10 locus conserved noncoding sequence 3 site and that it activates gene expression in a luciferase reporter assay and following retroviral transduction. Etv5 deficiency did not affect the expression of other transcription factors known to be important for expression of IL-10, including Jun family members, GATA3, E4BP4, and IFN regulatory factor 4. However, in the absence of Etv5, binding of these transcription factors to the Il10 locus was dramatically reduced. Ectopic Etv5 expression in Th2 cells that lack Etv5 restored IL-10 production and the binding of IL-10–inducing transcription factors including E4BP4, IFN regulatory factor 4, and GATA3. Taken together, we conclude that Etv5 plays a crucial role in regulating IL-10 production in Th2 cells by facilitating the binding of IL-10–inducing transcription factors at the Il10 locus.

http://ift.tt/2llaJa8

Diet-Derived Short Chain Fatty Acids Stimulate Intestinal Epithelial Cells To Induce Mucosal Tolerogenic Dendritic Cells [MUCOSAL IMMUNOLOGY]

The gastrointestinal tract is continuously exposed to many environmental factors that influence intestinal epithelial cells and the underlying mucosal immune system. In this article, we demonstrate that dietary fiber and short chain fatty acids (SCFAs) induced the expression of the vitamin A–converting enzyme RALDH1 in intestinal epithelial cells in vivo and in vitro, respectively. Furthermore, our data showed that the expression levels of RALDH1 in small intestinal epithelial cells correlated with the activity of vitamin A–converting enzymes in mesenteric lymph node dendritic cells, along with increased numbers of intestinal regulatory T cells and a higher production of luminal IgA. Moreover, we show that the consumption of dietary fiber can alter the composition of SCFA-producing microbiota and SCFA production in the small intestines. In conclusion, our data illustrate that dietary adjustments affect small intestinal epithelial cells and can be used to modulate the mucosal immune system.

http://ift.tt/2l5EIQX

Plant Lectins Activate the NLRP3 Inflammasome To Promote Inflammatory Disorders [INNATE IMMUNITY AND INFLAMMATION]

Plant-derived dietary lectins have been reported to be involved in the pathogenesis of several inflammatory diseases, including inflammatory bowel disease, diabetes, rheumatoid arthritis, and celiac disease, but little is known about the molecular mechanisms underlying lectin-induced inflammation. In this study, we showed that plant lectins can induce caspase-1 activation and IL-1β secretion via the NLRP3 inflammasome. Lectins were internalized and subsequently escaped from the lysosome and then translocated to the endoplasmic reticulum. Endoplasmic reticulum–loaded plant lectins then triggered Ca²⁺ release and mitochondrial damage, and inhibition of Ca²⁺ release and mitochondrial reactive oxygen species by chemical inhibitors significantly suppressed NLRP3 inflammasome activation. In vivo, plant lectin–induced inflammation and tissue damage also depended on the NLRP3 inflammasome. Our findings indicate that plant lectins can act as an exogenous "danger signal" that can activate the NLRP3 inflammasome and suggest that dietary lectins might promote inflammatory diseases via the NLRP3 inflammasome.

http://ift.tt/2l5Noqt

Sex Drives Dimorphic Immune Responses to Viral Infections [BRIEF REVIEWS]

New attention to sexual dimorphism in normal mammalian physiology and disease has uncovered a previously unappreciated breadth of mechanisms by which females and males differentially exhibit quantitative phenotypes. Thus, in addition to the established modifying effects of hormones, which prenatally and postpubertally pattern cells and tissues in a sexually dimorphic fashion, sex differences are caused by extragonadal and dosage effects of genes encoded on sex chromosomes. Sex differences in immune responses, especially during autoimmunity, have been studied predominantly within the context of sex hormone effects. More recently, immune response genes have been localized to sex chromosomes themselves or found to be regulated by sex chromosome genes. Thus, understanding how sex impacts immunity requires the elucidation of complex interactions among sex hormones, sex chromosomes, and immune response genes. In this Brief Review, we discuss current knowledge and new insights into these intricate relationships in the context of viral infections.

http://ift.tt/2ll7ks9

Cutting Edge: Helicobacter pylori Induces Nuclear Hypersegmentation and Subtype Differentiation of Human Neutrophils In Vitro [CUTTING EDGE]

Helicobacter pylori infects the human stomach and causes a spectrum of disease that includes gastritis, peptic ulcers, and gastric adenocarcinoma. A chronic, neutrophil-rich inflammatory response characterizes this infection. It is established that H. pylori stimulates neutrophil chemotaxis and a robust respiratory burst, but other aspects of this interaction are incompletely defined. We demonstrate here that H. pylori induces N1-like subtype differentiation of human neutrophils as indicated by profound nuclear hypersegmentation, a CD62L^dim, CD16^bright, CD11b^bright, CD66b^bright, CD63^bright surface phenotype, proinflammatory cytokine secretion, and cytotoxicity. Hypersegmentation requires direct neutrophil–H. pylori contact as well as transcription and both host and bacterial protein synthesis, but not urease, NapA, VacA, CagA, or CagT. The concept of neutrophil plasticity is new and, to our knowledge, these data are the first evidence that neutrophils can undergo subtype differentiation in vitro in response to bacterial pathogen infection. We hypothesize that these changes favor H. pylori persistence and disease.

http://ift.tt/2l5GPnH

Circulating Monocytes Exhibit an Endotoxin Tolerance Status after Acute Ischemic Stroke: Mitochondrial DNA as a Putative Explanation for Poststroke Infections [INNATE IMMUNITY AND INFLAMMATION]

Patients with acute ischemic stroke (AIS) suffer from infections associated with mortality. The relevance of the innate immune system, and monocytes in particular, has emerged as an important factor in the evolution of these infections. The study enrolled 14 patients with AIS, without previous treatment, and 10 healthy controls. In the present study, we show that monocytes from patients with AIS exhibit a refractory state or endotoxin tolerance. The patients were unable to orchestrate an inflammatory response against LPS and expressed three factors reported to control the evolution of human monocytes into a refractory state: IL-1R–associated kinase-M, NFkB2/p100, and hypoxia-inducible factor-1α. The levels of circulating mitochondrial DNA (mtDNA) in patients with AIS correlated with impaired inflammatory response of isolated monocytes. Interestingly, the patients could be classified into two groups: those who were infected and those who were not, according to circulating mtDNA levels. This finding was validated in an independent cohort of 23 patients with AIS. Additionally, monocytes from healthy controls, cultured in the presence of both sera from patients and mtDNA, reproduced a refractory state after endotoxin challenge. This effect was negated by either a TLR9 antagonist or DNase treatment. The present data further extend our understanding of endotoxin tolerance implications in AIS. A putative role of mtDNA as a new biomarker of stroke-associated infections, and thus a clinical target for preventing poststroke infection, has also been identified.

http://ift.tt/2l5GOA9

Cutting Edge: Notch Signaling Promotes the Plasticity of Group-2 Innate Lymphoid Cells [CUTTING EDGE]

The mechanisms underlying lymphocyte lineage stability and plasticity remain elusive. Recent work indicates that innate lymphoid cells (ILC) possess substantial plasticity. Whereas natural ILC2 (nILC2) produce type-2 cytokines, plastic inflammatory ILC2 (iILC2) can coproduce both type-2 cytokines and the ILC3-characteristic cytokine, IL-17. Mechanisms that elicit this lineage plasticity, and the importance in health and disease, remain unclear. In this study we show that iILC2 are potent inducers of airway inflammation in response to acute house dust mite challenge. We find that Notch signaling induces lineage plasticity of mature ILC2 and drives the conversion of nILC2 into iILC2. Acute blockade of Notch signaling abolished functional iILC2, but not nILC2, in vivo. Exposure of isolated nILC2 to Notch ligands induced Rorc expression and elicited dual IL-13/IL-17 production, converting nILC2 into iILC2. Together these results reveal a novel role for Notch signaling in eliciting ILC2 plasticity and driving the emergence of highly proinflammatory innate lymphocytes.

http://ift.tt/2ll8kfA

Identification of Motile Sperm Domain-Containing Protein 2 as Regulator of Human Monocyte Migration [INNATE IMMUNITY AND INFLAMMATION]

Binding of chemokines to their cognate receptors on monocytes instigates a cascade of events that directs these cells to migrate to sites of inflammation and cancerous tissues. Although targeting of selected chemokine receptors on monocytes exhibited preclinical efficacy, attempts to translate these studies to the clinic have failed thus far, possibly due to redundancy of the target receptor. We reveal that motile sperm domain–containing protein 2 (MOSPD2), a protein with a previously unknown function, regulates monocyte migration in vitro. This protein was found to be expressed on the cytoplasmic membrane of human monocytes. Silencing or neutralizing MOSPD2 in monocytes restricted their migration when induced by different chemokines. Mechanistically, silencing MOSPD2 inhibited signaling events following chemokine receptor ligation. When tested for expression in other immune cell subsets, MOSPD2 was apparent also, though less abundantly, in neutrophils, but not in lymphocytes. Thus, in the presence of neutralizing Abs, neutrophil migration was inhibited to some extent whereas lymphocyte migration remained intact. In view of these results, we suggest MOSPD2 as a potential target protein for treating diseases in which monocyte and neutrophil accumulation is correlated with pathogenesis.

http://ift.tt/2l5uhga

Induction of IL21 in Peripheral T Follicular Helper Cells Is an Indicator of Influenza Vaccine Response in a Previously Vaccinated HIV-Infected Pediatric Cohort [INFECTIOUS DISEASE AND HOST RESPONSE]

HIV-infected patients of all ages frequently underperform in response to seasonal influenza vaccination, despite virologic control of HIV. The molecular mechanisms governing this impairment, as well as predictive biomarkers for responsiveness, remain unknown. This study was performed in samples obtained prevaccination (T0) from HIV-infected children who received the 2012–2013 seasonal influenza vaccine. Response status was determined based on established criterion for hemagglutination inhibition titer; participants with a hemagglutination titer ≥1:40 plus a ≥4-fold increase over T0 at 3 wk postvaccination were designated as responders. All children had a history of prior influenza vaccinations. At T0, the frequencies of CD4 T cell subsets, including peripheral T follicular helper (pTfh) cells, which provide help to B cells for developing into Ab-secreting cells, were similar between responders and nonresponders. However, in response to in vitro stimulation with influenza A/California/7/2009 (H1N1) Ag, differential gene expression related to pTfh cell function was observed by Fluidigm high-density RT-PCR between responders and nonresponders. In responders, H1N1 stimulation at T0 also resulted in CXCR5 induction (mRNA and protein) in CD4 T cells and IL21 gene induction in pTfh cells that were strongly associated with H1N1-specific B cell responses postvaccination. In contrast, CD4 T cells of nonresponders exhibited increased expression of IL2 and STAT5 genes, which are known to antagonize peripheral Tfh cell function. These results suggest that the quality of pTfh cells at the time of immunization is important for influenza vaccine responses and provide a rationale for targeted, ex vivo Ag-driven molecular profiling of purified immune cells to detect predictive biomarkers of the vaccine response.

http://ift.tt/2l5MBpk

Semaphorin 3E Deficiency Exacerbates Airway Inflammation, Hyperresponsiveness, and Remodeling in a Mouse Model of Allergic Asthma [ALLERGY AND OTHER HYPERSENSITIVITIES]

Semaphorin 3E (Sema3E) plays a crucial role in axon guidance, vascular patterning, and immune regulation. Nevertheless, the role of Sema3E in asthma is still elusive. In this study, we show that genetic ablation of Sema3E in mice results in increased lung granulocytosis, airway hyperresponsiveness, mucus overproduction, collagen deposition, and Th2/Th17 inflammation. Transfer of Sema3e^–/– bone marrow progenitor cells to irradiated wild-type (WT) recipients exacerbates airway hyperresponsiveness and inflammation, whereas transfer of WT bone marrow progenitor cells ameliorates asthma pathology in Sema3e^–/– recipients. Sema3e^–/– mice display a higher frequency of CD11b⁺ pulmonary dendritic cells than their WT controls at the baseline and after sensitization with house dust mite. Adoptive transfer of CD11b⁺ pulmonary dendritic cells from Sema3e^–/– mice into WT recipients increases house dust mite–induced Th2/Th17 inflammation in the airway. Together, these findings identify Sema3E as a novel regulatory molecule in allergic asthma that acts upstream of proallergic events and suggest that targeting this molecule could be a novel approach to treat allergic asthma.

http://ift.tt/2l5pwU4

IL-4 Haploinsufficiency Specifically Impairs IgE Responses against Allergens in Mice [ALLERGY AND OTHER HYPERSENSITIVITIES]

Polymorphisms in genes involved in IL-4 responses segregate with allergic disease risk and correlate with IgE levels in humans, and IL-4 promotes IgE and IgG1 Ab production against allergens in mice. We report that mice with only one intact Il4 gene copy are significantly impaired in their ability to make specific IgE responses against allergens, whereas IgG1 responses to allergens remain unaffected. Il4-hemizygosity also resulted in a modest but detectable drop in IL-4 production by CD4⁺ T cells isolated from lymph nodes and prevented IgE-dependent oral allergen–induced diarrhea. We conclude that a state of haploinsufficiency for the Il4 gene locus is specifically relevant for IL-4–dependent IgE responses to allergens with the amount of IL-4 produced in the hemizygous condition falling close to the threshold required for switching to IgE production. These results may be relevant for how polymorphisms in genes affecting IL-4 responses influence the risk of IgE-mediated allergic disease in humans.

http://ift.tt/2ll5QOo