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 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

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

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

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

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

Customized software to optimize circumferential pharyngoesophageal free flap reconstruction

http://ift.tt/2ltRM3n

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

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

Customized software to optimize circumferential pharyngoesophageal free flap reconstruction

http://ift.tt/2ltRM3n

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

http://ift.tt/2llzS4J

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

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

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

Comparative study of two models of combined pulmonary fibrosis and emphysema in mice

Publication date: Available online 21 February 2017
Source:Acta Histochemica
Author(s): Wan-Guang Zhang, Si-Si Wu, Li He, Qun Yang, Yi-Kuan Feng, Yue-Tao Chen, Guo-Hua Zhen, Yong-Jian Xu, Zhen-Xiang Zhang, Jian-Ping Zhao, Hui-Lan Zhang
Combined pulmonary fibrosis and emphysema (CPFE) is an "umbrella term" encompassing emphysema and pulmonary fibrosis, but its pathogenesis is not known. We established two models of CPFE in mice using tracheal instillation with bleomycin (BLM) or murine gammaherpesvirus 68 (MHV-68). Experimental mice were divided randomly into four groups: A (normal control, n=6), B (emphysema, n=6), C (emphysema+MHV-68, n=24), D (emphysema+BLM, n=6). Group C was subdivided into four groups: C1 (sacrificed on day 367, 7 days after tracheal instillation of MHV-68); C2 (day 374; 14days); C3 (day 381; 21days); C4 (day 388; 28days). Conspicuous emphysema and interstitial fibrosis were observed in BLM and MHV-68 CPFE mouse models. However, BLM induced diffuse pulmonary interstitial fibrosis with severely diffuse pulmonary inflammation; MHV-68 induced relatively modest inflammation and fibrosis, and the inflammation and fibrosis were not diffuse, but instead around bronchioles. Inflammation and fibrosis were detectable in the day-7 subgroup and reached a peak in the day-28 subgroup in the emphysema + MHV-68 group. Levels of macrophage chemoattractant protein-1, macrophage inflammatory protein-1α, interleukin-13, and transforming growth factor-β1 in bronchoalveolar lavage fluid were increased significantly in both models. Percentage of apoptotic type-2 lung epithelial cells was significantly higher; however, all four types of cytokine and number of macrophages were significantly lower in the emphysema+MHV-68 group compared with the emphysema +BLM group. The different changes in pathology between BLM and MHV-68 mice models demonstrated different pathology subtypes of CPFE: macrophage infiltration and apoptosis of type-II lung epithelial cells increased with increasing pathology score for pulmonary fibrosis.



http://ift.tt/2kY3zp1

Wnt-1 immunodetection in the regenerating tail of lizard suggests it is involved in the proliferation and distal growth of the blastema

Publication date: Available online 21 February 2017
Source:Acta Histochemica
Author(s): Lorenzo Alibardi
Lizard tail regeneration depends from growth of the apical tip and autonomous regeneration of a new spinal cord, cartilaginous tube and muscles. The presence of embryonic signaling pathways is likely involved and we have focused on immunolocalization of Wnt1 protein in regenerating tissues, a protein promoting proliferation and tumorigenesis. Western blot indicates some immunoreactive bands in the expected range at 46 and 33kDa in the regenerating tail. Immunolocalization indicates that Wnt1 is prevalently detected in the apical wound epidermis, blastema, and ependyma ampulla of the regenerating tail while it lowers in other tissues of more proximal regions close to the original tail stump. Although a gradient for Wnt1 was not detected, the higher immunofluorescence present in the apical region of the blastema and around the regenerating spinal cord indicates that the protein could be secreted from the apical wound epidermis and the ependyma and might influence cell proliferation in the blastema, the distal-most growing center of the new tail. The present observations suggest the involvement of the Wnt pathway to direct the process of tail regeneration in lizard. The stimulation of proliferation of epidermal and mesenchymal cells in the apical blastema by Wnt proteins remains to be experimentally validated.



http://ift.tt/2lm55EC

Gradual decrease in spermatogenesis caused by chronic stress

Publication date: Available online 21 February 2017
Source:Acta Histochemica
Author(s): Lizbeth Juárez-Rojas, Rosa María Vigueras-Villaseñor, Fahiel Casillas, Socorro Retana-Márquez
Chronic stress induces decreased sperm motility, viability and concentration in stressed males. Also, stress modifies oxidative status and causes apoptosis in testes, as well as a decrease in the epithelial area of seminiferous tubules. However, there are no studies that analyze the alterations caused by stress in testicular cells. Thus, in this study, alterations in the morphology of testicular germ cells caused by different days of chronic stress were assessed. Adult male rats were exposed to stress by immersion in cold water (ICW) daily for 3, 8, 20 or 50 consecutive days. Plasma testosterone and corticosterone were also assessed. Results showed that chronic stress causes loss of germ cells, and alteration of spermatogenesis. Seminiferous tubules from stressed males showed several degenerative signs, such as vacuoles in the basal epithelium, with picnotic indicia; moderate to severe exfoliation of degenerative germinal cells in the tubule lumen was also observed. These alterations were observed in all days of stress in a gradual way, from day 3–50. Testosterone levels were decreased at all those times, and corticosterone concentrations were increased on the same days. These results show that chronic stress causes severe damage to germ cells, which can account for infertility problems in males. These alterations are related to a decrease in testosterone as well as an increase in corticosterone caused by stress.



http://ift.tt/2kXZz7I

Neuronal differentiation in the early human retinogenesis

Publication date: Available online 20 February 2017
Source:Acta Histochemica
Author(s): Anita Rancic, Natalija Filipovic, Josipa Marin Lovric, Snjezana Mardesic, Mirna Saraga-Babic, Katarina Vukojevic
AimOur study investigates the differentiation of retinal stem cells towards different neuronal subtypes during the critical period of human eye development.MethodsExpression of the neuronal marker neurofilament 200 (NF200), tyrosine hydroxilase (TH) and choline acetyltransferase (ChAT) was seen by immunofluorescence in the 5th–12th – week stage of development in the human eye. Data was analysed by Mann–Whitney, Kruskal–Wallis and Dunn's post hoc tests.ResultsNF200, TH and ChAT cells appeared in the 5th/6th week and gradually increased during further development. The proportion of TH positive areas were distributed similarly to NF200, with a higher proportion in the outer neuroblastic layer. The proportion of a ChAT positive surface was highest in the 5th/6th – week whilst from the 7th week onwards, its proportion became higher in the optic nerve and inner neuroblastic layers than in the outer layer, where a decrease of ChAT positive areas were seen.ConclusionsOur study indicates a high differentiation potential of early retinal cells, which decreased with the advancement of development. The observed great variety of retinal phenotypic expressions results from a large scale of influences, taking place at different developmental stages.



http://ift.tt/2lmbJuT

Sonoelastomics for Breast Tumor Classification: A Radiomics Approach with Clustering-Based Feature Selection on Sonoelastography

Publication date: Available online 21 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Qi Zhang, Yang Xiao, Jingfeng Suo, Jun Shi, Jinhua Yu, Yi Guo, Yuanyuan Wang, Hairong Zheng
A radiomics approach to sonoelastography, called "sonoelastomics," is proposed for classification of benign and malignant breast tumors. From sonoelastograms of breast tumors, a high-throughput 364-dimensional feature set was calculated consisting of shape features, intensity statistics, gray-level co-occurrence matrix texture features and contourlet texture features, which quantified the shape, hardness and hardness heterogeneity of a tumor. The high-throughput features were then selected for feature reduction using hierarchical clustering and three-feature selection metrics. For a data set containing 42 malignant and 75 benign tumors from 117 patients, seven selected sonoelastomic features achieved an area under the receiver operating characteristic curve of 0.917, an accuracy of 88.0%, a sensitivity of 85.7% and a specificity of 89.3% in a validation set via the leave-one-out cross-validation, revealing superiority over the principal component analysis, deep polynomial networks and manually selected features. The sonoelastomic features are valuable in breast tumor differentiation.



http://ift.tt/2ltFqsk

Investigation of Ultrasound-Measured Flow Velocity, Flow Rate and Wall Shear Rate in Radial and Ulnar Arteries Using Simulation

Publication date: Available online 21 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Xiaowei Zhou, Chunming Xia, Gandy Stephen, Faisel Khan, George A. Corner, Peter R. Hoskins, Zhihong Huang
Parameters of blood flow measured by ultrasound in radial and ulnar arteries, such as flow velocity, flow rate and wall shear rate, are widely used in clinical practice and clinical research. Investigation of these measurements is useful for evaluating accuracy and providing knowledge of error sources. A method for simulating the spectral Doppler ultrasound measurement process was developed with computational fluid dynamics providing flow-field data. Specific scanning factors were adjusted to investigate their influence on estimation of the maximum velocity waveform, and flow rate and wall shear rate were derived using the Womersley equation. The overestimation in maximum velocity increases greatly (peak systolic from about 10% to 30%, time-averaged from about 30% to 50%) when the beam–vessel angle is changed from 30° to 70°. The Womersley equation was able to estimate flow rate in both arteries with less than 3% error, but performed better in the radial artery (2.3% overestimation) than the ulnar artery (15.4% underestimation) in estimating wall shear rate. It is concluded that measurements of flow parameters in the radial and ulnar arteries with clinical ultrasound scanners are prone to clinically significant errors.



http://ift.tt/2kKro8t

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

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

Effects of Two Diode Lasers With and Without Photosensitization on Contaminated Implant Surfaces: An Ex Vivo Study

Photomedicine and Laser Surgery , Vol. 0, No. 0.


http://ift.tt/2kXS0ht

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

Mismatch field latency, but not power, may mark a shared autistic and schizotypal trait phenotype.

Publication date: Available online 21 February 2017
Source:International Journal of Psychophysiology
Author(s): Talitha C. Ford, Will Woods, David P. Crewther
The auditory mismatch negativity (MMN), a preattentive processing potential, and its magnetic counterpart (MMF) are consistently reported as reduced in schizophrenia and autism spectrum disorders. This study investigates whether MMF characteristics differ between subclinically high and low scorers on the recently discovered shared autism and schizophrenia phenotype, Social Disorganisation.A total of 18 low (10 female) and 19 high (9 female) Social Disorganisation scorers underwent magnetoencephalography (MEG) during a MMF paradigm of 50ms standard (1000Hz, 85%) and 100ms duration deviant tones. MMF was measured from the strongest active magnetometer over the right and left hemispheres (consistent across groups) after 100ms.No differences in MMF power were found, however there was a significant delay in the MMF peak (p= 0.007). The P3am (following the MMF) was significantly reduced across both hemispheres for the high Social Disorganisation group (p= 0.025), there were no specific hemispheric differences in P3am power or latency. Right MMF peak latency increased with higher scores on the schizotypal subscales Odd Speech, Odd Behaviour and Constricted Affect.Findings suggest that MMF peak latency delay marks a convergence of the autism and schizophrenia spectra at a subclinical. These findings have significant implications for future research methodology, as well as clinical practice.



http://ift.tt/2ltCz2t

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Bhushan P. Mahadik, Narayanan A.K. Bharadwaj, Randy H. Ewoldt, Brendan A.C. Harley
Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin⁺) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin⁺ cells increased myeloid differentiation. We report thresholds where autocrine vs. paracrine cues alter HSC fate transitions, and were able to selectively abrogate the effects of matrix diffusivity and niche cell co-culture via the use of inhibitory cocktails of autocrine or paracrine signals. Together, these results suggest diffusive biotransport in three-dimensional biomaterials are a critical design element for the development of a synthetic stem cell niche.



http://ift.tt/2llW0fm

A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): H.K. Awada, D.W. Long, Z. Wang, M.P. Hwang, K. Kim, Y. Wang
After myocardial infarction (MI), the heart undergoes fibrotic pathological remodeling instead of repair and regeneration. With multiple pathologies developing after MI, treatment using several proteins is expected to address this range of pathologies more effectively than a single-agent therapy. A factorial design of experiments study guided us to combine three complementary factors in one injection: tissue inhibitor of metalloproteinases-3 (TIMP-3) was embedded in a fibrin gel for signaling in the initial phase of the treatment, while basic fibroblast growth factor (FGF-2) and stromal cell-derived factor 1-alpha (SDF-1α) were embedded in heparin-based coacervates for sustained release and distributed within the same fibrin gel to exert their effects over a longer period. The gel was then tested in a rat model of myocardial infarction. Contractility of rat hearts treated with the protein coacervate-gel composite stabilized and slightly improved after the first week while contractility continued to decrease in rats treated with free proteins or saline over the 8 week study period. Hearts receiving the protein coacervate-gel composite treatment also exhibited reduced ventricular dilation, inflammation, fibrosis, and extracellular matrix (ECM) degradation. Revascularization, cardiomyocyte preservation, stem cell homing, and increased myocardial strain likely all contributed to the repair. This study demonstrates the potential of a multifactorial therapeutic approach in MI, using three complementary proteins delivered sequentially for comprehensive healing. The study also shows the necessity of controlled delivery for growth factors and cytokines to be an effective treatment.



http://ift.tt/2kXMZ8F

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Stefano Persano, Maria L. Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell. This core-shell structured mRNA vaccine enters dendritic cells through macropinocytosis. It displayed intrinsic adjuvant activity by potently stimulating interferon-β and interleukin-12 expression in dendritic cells through Toll-like receptor 7/8 signaling. Dendritic cells treated with the mRNA vaccine displayed enhanced antigen presentation capability. Mice bearing lung metastatic B16-OVA tumors expressing the ovalbumin antigen were treated with the lipopolyplex mRNA, and over 90% reduction of tumor nodules was observed. Collectively, this core-shell structure offers a promising platform for mRNA vaccine development.



http://ift.tt/2llWO3E

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

Nutritional status and metabolic profile in neurologically impaired pediatric surgical patients

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2kKgoYI

Non-HDL-cholesterol and C-reactive protein in children and adolescents with type 1 diabetes

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2maCel3

Vascular risk factors are associated with retinal arteriolar narrowing and venular widening in children and adolescents with type 1 diabetes

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2kKbQkW

Unexplained cyanosis caused by hepatopulmonary syndrome in a girl with APECED syndrome

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2maz8gS

Three cases of Gordon syndrome with dominant KLHL3 mutations

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2kKjfkt

A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2maFWvl

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.


http://ift.tt/2kKk6BF

Erratum

http://ift.tt/2l6hQ3E

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.

http://ift.tt/2l6quz9

Erratum

http://ift.tt/2l6nYsX

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

http://ift.tt/2lEi8lm

Erratum

http://ift.tt/2lEnZXQ

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

http://ift.tt/2lEngGr

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

http://ift.tt/2l6l3Al

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

http://ift.tt/2lEo5id

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

http://ift.tt/2l6h86z

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

http://ift.tt/2lEqLwf

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

http://ift.tt/2l6eu0x

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

http://ift.tt/2l61M20

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

http://ift.tt/2lEf34T

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

http://ift.tt/2lEAOBx

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

http://ift.tt/2l68vcp

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

http://ift.tt/2lEes3d

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Stefano Persano, Maria L. Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell. This core-shell structured mRNA vaccine enters dendritic cells through macropinocytosis. It displayed intrinsic adjuvant activity by potently stimulating interferon-β and interleukin-12 expression in dendritic cells through Toll-like receptor 7/8 signaling. Dendritic cells treated with the mRNA vaccine displayed enhanced antigen presentation capability. Mice bearing lung metastatic B16-OVA tumors expressing the ovalbumin antigen were treated with the lipopolyplex mRNA, and over 90% reduction of tumor nodules was observed. Collectively, this core-shell structure offers a promising platform for mRNA vaccine development.



http://ift.tt/2llWO3E

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

http://ift.tt/2lEngGr

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Bhushan P. Mahadik, Narayanan A.K. Bharadwaj, Randy H. Ewoldt, Brendan A.C. Harley
Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin⁺) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin⁺ cells increased myeloid differentiation. We report thresholds where autocrine vs. paracrine cues alter HSC fate transitions, and were able to selectively abrogate the effects of matrix diffusivity and niche cell co-culture via the use of inhibitory cocktails of autocrine or paracrine signals. Together, these results suggest diffusive biotransport in three-dimensional biomaterials are a critical design element for the development of a synthetic stem cell niche.



http://ift.tt/2llW0fm

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

http://ift.tt/2l61Oa2

For the Patient

http://ift.tt/2l6iwpT

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

http://ift.tt/2lEi8lm

A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): H.K. Awada, D.W. Long, Z. Wang, M.P. Hwang, K. Kim, Y. Wang
After myocardial infarction (MI), the heart undergoes fibrotic pathological remodeling instead of repair and regeneration. With multiple pathologies developing after MI, treatment using several proteins is expected to address this range of pathologies more effectively than a single-agent therapy. A factorial design of experiments study guided us to combine three complementary factors in one injection: tissue inhibitor of metalloproteinases-3 (TIMP-3) was embedded in a fibrin gel for signaling in the initial phase of the treatment, while basic fibroblast growth factor (FGF-2) and stromal cell-derived factor 1-alpha (SDF-1α) were embedded in heparin-based coacervates for sustained release and distributed within the same fibrin gel to exert their effects over a longer period. The gel was then tested in a rat model of myocardial infarction. Contractility of rat hearts treated with the protein coacervate-gel composite stabilized and slightly improved after the first week while contractility continued to decrease in rats treated with free proteins or saline over the 8 week study period. Hearts receiving the protein coacervate-gel composite treatment also exhibited reduced ventricular dilation, inflammation, fibrosis, and extracellular matrix (ECM) degradation. Revascularization, cardiomyocyte preservation, stem cell homing, and increased myocardial strain likely all contributed to the repair. This study demonstrates the potential of a multifactorial therapeutic approach in MI, using three complementary proteins delivered sequentially for comprehensive healing. The study also shows the necessity of controlled delivery for growth factors and cytokines to be an effective treatment.



http://ift.tt/2kXMZ8F

Erratum

http://ift.tt/2l6hQ3E

Erratum

http://ift.tt/2lEnZXQ

Erratum

http://ift.tt/2l6nYsX

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

http://ift.tt/2l6h86z

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

http://ift.tt/2l6l3Al

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

http://ift.tt/2lEo5id

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

http://ift.tt/2lEqLwf

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

http://ift.tt/2l6eu0x

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

http://ift.tt/2lEf34T

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

http://ift.tt/2l61M20

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

http://ift.tt/2lEAOBx

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

http://ift.tt/2l68vcp

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

http://ift.tt/2lEes3d

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

http://ift.tt/2l61Oa2

For the Patient

http://ift.tt/2l6iwpT

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.

http://ift.tt/2l6quz9

Ejection Fraction: Misunderstood and Overrated (Changing the Paradigm in Categorizing Heart Failure).

Author: Konstam, Marvin A. MD; Abboud, Francois M. MD

Page: 717-719

http://ift.tt/2marTWu

Looking Back at Look AHEAD Through the Lens of Recent Diabetes Outcome Trials.

Author: Belalcazar, L. Maria MD; Ballantyne, Christie M. MD

Page: 720-723

http://ift.tt/2kKhVOl

Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients With Heart Failure and Preserved Ejection Fraction: A Report From the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction).

Author: Kristensen, Soren L. MD, PhD; Mogensen, Ulrik M. MD, PhD; Jhund, Pardeep S. MBChB, MSc, PhD; Petrie, Mark C. MB ChB; Preiss, David MD, PhD; Win, Sithu MD; Kober, Lars MD, DMSc; McKelvie, Robert S. MD, PhD; Zile, Michael R. MD; Anand, Inder S. MD, DPhil (Oxon); Komajda, Michel MD; Gottdiener, John S. MD; Carson, Peter E. MD; McMurray, John J. V. MD

Page: 724-735

http://ift.tt/2maqcZa

The Diabetic Heart Failure With Preserved Ejection Fraction Phenotype: Is it Real and Is It Worth Targeting Therapeutically?.

Author: Lindman, Brian R. MD, MSc

Page: 736-740

http://ift.tt/2kKnXyu

Genetic Obesity and the Risk of Atrial Fibrillation: Causal Estimates from Mendelian Randomization.

Author: Chatterjee, Neal A. MD; Giulianini, Franco PhD; Geelhoed, Bastiaan PhD; Lunetta, Kathryn L. PhD; Misialek, Jeffrey R. MPH; Niemeijer, Maartje N. MD, MSc; Rienstra, Michiel MD, PhD; Rose, Lynda M. MS; Smith, Albert V. PhD; Arking, Dan E. PhD; Ellinor, Patrick T. MD, PhD; Heeringa, Jan MD, PhD; Lin, Honghuang PhD; Lubitz, Steven A. MD, MPH; Soliman, Elsayed Z. MD, MSc; Verweij, Niek PhD; Alonso, Alvaro MD, PhD; Benjamin, Emelia J. MD, ScM; Gudnason, Vilmundur MD, PhD; Stricker, Bruno H. C. MMed, PhD; Van Der Harst, Pim MD, PhD; Chasman, Daniel I. PhD; Albert, Christine M. MD, MPH

Page: 741-754

http://ift.tt/2mazPqO

Mendelian Randomization: Using Natural Genetic Variation to Assess the Causal Role of Modifiable Risk Factors in Observational Studies.

Author: Neeland, Ian J. MD; Kozlitina, Julia PhD

Page: 755-758

http://ift.tt/2kKmrg3

Prevalence, Incidence, and Mortality of Stroke in China: Results from a Nationwide Population-Based Survey of 480 687 Adults.

Author: Wang, Wenzhi MD; Jiang, Bin MD; Sun, Haixin MD, PhD; Ru, Xiaojuan PhD; Sun, Dongling PhD; Wang, Linhong MD; Wang, Limin MD; Jiang, Yong MD; Li, Yichong PhD; Wang, Yilong MD, PhD; Chen, Zhenghong PhD; Wu, Shengping MD; Zhang, Yazhuo MD; Wang, David DO; Wang, Yongjun MD; Feigin, Valery L. MD, PhD; for the NESS-China Investigators

Page: 759-771

http://ift.tt/2maAmcd

Risk Factors for Coarctation of the Aorta on Prenatal Ultrasound: A Systematic Review and Meta-Analysis.

Author: Familiari, Alessandra MD; Morlando, Maddalena MD; Khalil, Asma MD; Sonesson, Sven-Erik MD, PhD; Scala, Carolina MD; Rizzo, Giuseppe MD; Del Sordo, Gelsomina MD; Vassallo, Chiara MD; Elena Flacco, Maria MD; Manzoli, Lamberto MD; Lanzone, Antonio MD, PhD; Scambia, Giovanni MD, PhD; Acharya, Ganesh MD, PhD; D'Antonio, Francesco MD, PhD

Page: 772-785

http://ift.tt/2kKfYBM

Functional Definition of Progenitors Versus Mature Endothelial Cells Reveals Key SoxF-Dependent Differentiation Process.

Author: Patel, Jatin PhD; Seppanen, Elke J. PhD; Rodero, Mathieu P. PhD; Wong, Ho Yi BSc; Donovan, Prudence PhD; Neufeld, Zoltan PhD; Fisk, Nicholas M. MBBS, PhD; Francois, Mathias PhD; Khosrotehrani, Kiarash MD, PhD

Page: 786-805

http://ift.tt/2mahav0

Management of Pregnancy in Patients With Complex Congenital Heart Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association.

Author: Canobbio, Mary M. RN, MN, FAHA, Chair; Warnes, Carole A. MD, FRCP, Co-Chair; Aboulhosn, Jamil MD; Connolly, Heidi M. MD; Khanna, Amber MD; Koos, Brian J. MD, DPhil; Mital, Seema MD, FAHA, FRCPC; Rose, Carl MD; Silversides, Candice MD, FRCPC; Stout, Karen MD, FAHA; On behalf of the American Heart Association Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Functional Genomics and Translational Biology; and Council on Quality of Care and Outcomes Research

Page: e50-e87

http://ift.tt/2mawKXz