Allergen challenge increases capsaicin evoked cough responses in allergic asthma

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Imran Satia, Richard Watson, Tara Scime, Rachel J. Dockry, Shilpi Sen, James W. Ford, Patrick D. Mitchell, Stephen J. Fowler, Gail M. Gauvreau, Paul M. O'Byrne, Jaclyn A. Smith

Abstract

Background

Cough is a common and troublesome symptom in asthma but little is known about the neuronal pathways that trigger cough. The mechanisms by which airway inflammation, airway hyper-responsiveness and variable airflow obstruction cause cough are unclear.

Objective

To investigate the effects of allergen exposure on cough reflex sensitivity.

Methods

We performed a nine visit, randomised, single-blind, placebo-controlled, two-way cross-over study comparing cough responses to inhaled capsaicin in mild atopic asthmatics after allergen challenge compared with diluent control. Full dose capsaicin challenge was performed at screening to determine the excitatory dose evoking half the maximum cough response (ED₅₀), which was subsequently administered at 30mins and 24-hours after inhaled allergen/diluent challenge. Spontaneous coughing was measured for 24-hours after allergen/diluent. Methacholine challenge and induced sputum was performed before and after allergen/diluent challenge.

Results

Twelve steroid naïve subjects completed the study (6 female, mean age 34.8yrs) Allergen inhalation caused both an early (mean 38.2±S.D.13.0%) and late (23.7±13.2%) fall in FEV₁ and an increase in sputum eosinophils 24-hours later [median 1.9(IQR 0.8-5.8) % post-diluent to 14.9(8.9-37.3) % post-allergen, p=0.005]. There was also an increase in capsaicin evoked coughs after allergen exposure compared to diluent at both 30 mins [geometric mean coughs 21.9(95% C.I 16.5-29.20) versus 12.1(8.3-17.7), p<0.001], and at 24hrs [geometric mean coughs 16.1(95% C.I 11.3-23.0) versus 9.8(6.1-15.8), p=0.001]. Allergen exposure was also associated with an increase in spontaneous coughs over 24-hours.

Conclusion

Allergen induced bronchoconstriction and airway eosinophilia results in increased cough reflex sensitivity to capsaicin associated with an increase in 24-hour spontaneous coughing.

Graphical abstract

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Hematopoietic stem cell transplantation for CD40 ligand deficiency: results from an EBMT/ESID-IEWP-SCETIDE-PIDTC Study

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Francesca Ferrua, Stefania Galimberti, Virginie Courteille, Mary Anne Slatter, Claire Booth, Despina Moshous, Benedicte Neven, Stephane Blanche, Alexandra Laberko, Anna Shcherbina, Dmitry Balashov, Elena Soncini, Fulvio Porta, Hamoud Al-Mousa, Bandar Al-Saud, Hasan Al-Dhekri, Rand Arnaout, Renata Formankova, Yves Bertrand, Andrzej Lange

Abstract

Background

CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT).

Objective

We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics.

Methods

We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables relevance with respect to survival and cure.

Results

Overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) were 78.2%, 58.1% and 72.3% 5 years post-HSCT. Results were better in transplants performed ≥2000 and in children <10 years old at HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT ≤2 years from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC) and bone marrow-derived stem cells. Most rejections occurred after reduced intensity or non-myeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was ≥50% donor in 85.2%.

Conclusion

HSCT is curative in CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS and DFS. Prospective studies are required to compare risks of HSCT with those of life-long supportive therapy.

Graphical abstract

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Hypoxia Enhances CD8+ Tc2 Dependent Airway Hyperresponsiveness and Inflammation Through Hypoxia Inducible Factor 1α

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Fangkun Ning, Katsuyuki Takeda, Michaela Schedel, Joanne Domenico, Anthony Joetham, Erwin W. Gelfand

Abstract

Background

CD8+ T cells (Tc2) become potent, steroid-insensitive pathogenic effector cells in experimental asthma undergoing transcriptional reprogramming to IL-13 production in the presence of IL-4. However, no studies have described the effects of hypoxia exposure on Tc2 differentiation.

Objective

We determined the effects of hypoxia exposure on IL-13-producing CD8+ Tc2 cells.

Methods

CD8+ transgenic OT1 cells, differentiated with IL-2 and IL-4 (Tc2 cells) were exposed to normoxia (21% O₂) or hypoxia (3% O₂) and IL-13 production in vitro was monitored. Following differentiation under these conditions, cells were adoptively transferred into CD8-deficient mice and lung allergic responses including airway hyperesponsiveness to inhaled methacholine were assessed. The effects of pharmacologic inhibitors of hypoxia inducible factor 1α (HIF-1α) and HIF-2α were determined as were responses in HIF-1α-deficient OT1 cells.

Results

Under hypoxic conditioning, CD8+ Tc2 differentiation was significantly enhanced with increased numbers of IL-13+ T cells and increased production of IL-13 in vitro. Adoptive transfer of Tc2 cells differentiated under hypoxia restored lung allergic responses in sensitized and challenged CD8-deficient recipients to a greater degree than seen in recipients of Tc2 cells differentiated under normoxia. Pharmacologic inhibition of HIF-1α or genetic manipulation to reduce HIF-1α expression reduced the hypoxia-enhanced differentiation of Tc2 cells, IL-13 production, and the capacity of transferred cells to restore lung allergic responses in vivo. IL-4-dependent, hypoxia-mediated increases in HIF-1α and Tc2 differentiation were shown to be mediated through activation of JAK1/3 kinase and GATA3.

Conclusions

Hypoxia enhances CD8+ Tc2-dependent airway hyperresponsiveness and inflammation through activation of HIF-1α. These findings coupled with the known insensitivity of CD8+ T cells to corticosteroids suggests that activation of the IL-4-HIF-1α-IL-13 axis may play a role in the development of steroid-refractory asthma.

Graphical abstract

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Vitamin D is no substitute for the sun

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Yoshiaki Matsushima, Kento Mizutani, Yukie Yamaguchi, Keiichi Yamanaka

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Hm9p3R

Double-strand break repair through homologous recombination in autosomal recessive BCL10 deficiency

Publication date: Available online 18 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Sonia García-Gómez, Rebeca Chaparro, Amin Safa, Ana Van Den Rym, Rubén Martinez-Barricarte, Lazaro Lorenzo, Silvia Sánchez-Ramón, Victor Toledano, Carolina Cubillos-Zapata, Eduardo López-Collazo, Maria Dolores Martín-Arranz, Eduardo Martín-Arranz, Maria Vela, Pablo Gonzalez-Navarro, Antonio Pérez-Martínez, Jean-Laurent Casanova, Maria José Recio, Rebeca Pérez de Diego

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Challenges in Assessing the Efficacy of Systemic Corticosteroids for Severe Wheezing Episodes in Preschool Children

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Theresa W. Guilbert, Leonard B. Bacharier, David T. Mauger, Wanda Phipatanakul, Stanley J. Szefler, Susan Boehmer, Avraham Beigelman, Anne M. Fitzpatrick, Daniel J. Jackson, Sachin N. Baxi, Mindy Benson, Carey-Ann D. Burnham, Michael D. Cabana, Mario Castro, James F. Chmiel, Ronina Covar, Michael Daines, Jonathan M. Gaffin, Deborah A. Gentile, Fernando Holguin

Summary

This letter addresses the controversial issue of the use of oral corticosteroids during wheezing exacerbations in preschool-aged children by demonstrating findings of a prematurely terminated multi-center clinical trial, discussing lessons learned, and suggesting future directions.

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Allergen challenge increases capsaicin evoked cough responses in allergic asthma

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Imran Satia, Richard Watson, Tara Scime, Rachel J. Dockry, Shilpi Sen, James W. Ford, Patrick D. Mitchell, Stephen J. Fowler, Gail M. Gauvreau, Paul M. O'Byrne, Jaclyn A. Smith

Abstract

Background

Cough is a common and troublesome symptom in asthma but little is known about the neuronal pathways that trigger cough. The mechanisms by which airway inflammation, airway hyper-responsiveness and variable airflow obstruction cause cough are unclear.

Objective

To investigate the effects of allergen exposure on cough reflex sensitivity.

Methods

We performed a nine visit, randomised, single-blind, placebo-controlled, two-way cross-over study comparing cough responses to inhaled capsaicin in mild atopic asthmatics after allergen challenge compared with diluent control. Full dose capsaicin challenge was performed at screening to determine the excitatory dose evoking half the maximum cough response (ED₅₀), which was subsequently administered at 30mins and 24-hours after inhaled allergen/diluent challenge. Spontaneous coughing was measured for 24-hours after allergen/diluent. Methacholine challenge and induced sputum was performed before and after allergen/diluent challenge.

Results

Twelve steroid naïve subjects completed the study (6 female, mean age 34.8yrs) Allergen inhalation caused both an early (mean 38.2±S.D.13.0%) and late (23.7±13.2%) fall in FEV₁ and an increase in sputum eosinophils 24-hours later [median 1.9(IQR 0.8-5.8) % post-diluent to 14.9(8.9-37.3) % post-allergen, p=0.005]. There was also an increase in capsaicin evoked coughs after allergen exposure compared to diluent at both 30 mins [geometric mean coughs 21.9(95% C.I 16.5-29.20) versus 12.1(8.3-17.7), p<0.001], and at 24hrs [geometric mean coughs 16.1(95% C.I 11.3-23.0) versus 9.8(6.1-15.8), p=0.001]. Allergen exposure was also associated with an increase in spontaneous coughs over 24-hours.

Conclusion

Allergen induced bronchoconstriction and airway eosinophilia results in increased cough reflex sensitivity to capsaicin associated with an increase in 24-hour spontaneous coughing.

Graphical abstract

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Hematopoietic stem cell transplantation for CD40 ligand deficiency: results from an EBMT/ESID-IEWP-SCETIDE-PIDTC Study

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Francesca Ferrua, Stefania Galimberti, Virginie Courteille, Mary Anne Slatter, Claire Booth, Despina Moshous, Benedicte Neven, Stephane Blanche, Alexandra Laberko, Anna Shcherbina, Dmitry Balashov, Elena Soncini, Fulvio Porta, Hamoud Al-Mousa, Bandar Al-Saud, Hasan Al-Dhekri, Rand Arnaout, Renata Formankova, Yves Bertrand, Andrzej Lange

Abstract

Background

CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT).

Objective

We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics.

Methods

We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables relevance with respect to survival and cure.

Results

Overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) were 78.2%, 58.1% and 72.3% 5 years post-HSCT. Results were better in transplants performed ≥2000 and in children <10 years old at HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT ≤2 years from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC) and bone marrow-derived stem cells. Most rejections occurred after reduced intensity or non-myeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was ≥50% donor in 85.2%.

Conclusion

HSCT is curative in CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS and DFS. Prospective studies are required to compare risks of HSCT with those of life-long supportive therapy.

Graphical abstract

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Hjxqsv

Hypoxia Enhances CD8+ Tc2 Dependent Airway Hyperresponsiveness and Inflammation Through Hypoxia Inducible Factor 1α

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Fangkun Ning, Katsuyuki Takeda, Michaela Schedel, Joanne Domenico, Anthony Joetham, Erwin W. Gelfand

Abstract

Background

CD8+ T cells (Tc2) become potent, steroid-insensitive pathogenic effector cells in experimental asthma undergoing transcriptional reprogramming to IL-13 production in the presence of IL-4. However, no studies have described the effects of hypoxia exposure on Tc2 differentiation.

Objective

We determined the effects of hypoxia exposure on IL-13-producing CD8+ Tc2 cells.

Methods

CD8+ transgenic OT1 cells, differentiated with IL-2 and IL-4 (Tc2 cells) were exposed to normoxia (21% O₂) or hypoxia (3% O₂) and IL-13 production in vitro was monitored. Following differentiation under these conditions, cells were adoptively transferred into CD8-deficient mice and lung allergic responses including airway hyperesponsiveness to inhaled methacholine were assessed. The effects of pharmacologic inhibitors of hypoxia inducible factor 1α (HIF-1α) and HIF-2α were determined as were responses in HIF-1α-deficient OT1 cells.

Results

Under hypoxic conditioning, CD8+ Tc2 differentiation was significantly enhanced with increased numbers of IL-13+ T cells and increased production of IL-13 in vitro. Adoptive transfer of Tc2 cells differentiated under hypoxia restored lung allergic responses in sensitized and challenged CD8-deficient recipients to a greater degree than seen in recipients of Tc2 cells differentiated under normoxia. Pharmacologic inhibition of HIF-1α or genetic manipulation to reduce HIF-1α expression reduced the hypoxia-enhanced differentiation of Tc2 cells, IL-13 production, and the capacity of transferred cells to restore lung allergic responses in vivo. IL-4-dependent, hypoxia-mediated increases in HIF-1α and Tc2 differentiation were shown to be mediated through activation of JAK1/3 kinase and GATA3.

Conclusions

Hypoxia enhances CD8+ Tc2-dependent airway hyperresponsiveness and inflammation through activation of HIF-1α. These findings coupled with the known insensitivity of CD8+ T cells to corticosteroids suggests that activation of the IL-4-HIF-1α-IL-13 axis may play a role in the development of steroid-refractory asthma.

Graphical abstract

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Vitamin D is no substitute for the sun

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Yoshiaki Matsushima, Kento Mizutani, Yukie Yamaguchi, Keiichi Yamanaka

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Hm9p3R

Insulin-like growth factor 1 promotes cochlear synapse regeneration after excitotoxic trauma in vitro

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Kohei Yamahara, Nakarin Asaka, Tomoko Kita, Ippei Kishimoto, Mami Matsunaga, Norio Yamamoto, Koichi Omori, Takayuki Nakagawa

Abstract

In the context of acquired sensorineural hearing loss (SNHL), cochlear hair cells have long been thought to be among the most vulnerable elements in mammalian cochleae. However, recent studies have indicated that the synaptic connection between inner hair cells (IHC) and spiral ganglion neurons (SGN) can be an important target for the treatment of SNHL. Our previous studies in patients with sudden SNHL demonstrated delayed and gradual hearing recovery following topical application of insulin-like growth factor 1 (IGF-1), suggesting that not only protective but also regenerative mechanisms may account for hearing recovery after treatment with IGF-1. We then hypothesized that IGF-1 has the potential to drive the regeneration of IHC–SGN synapses. To test this hypothesis, we investigated the effects of IGF-1 on IHC–SGN synapses using cochlear explant cultures from postnatal day 2 mice that had been damaged by exposure to the excitatory amino acids N-methyl-d-aspartate and kainate. Cochlear explants that lost IHC–SGN synapses upon exposure to excitatory amino acids were cultured with exogenous IGF-1 for an additional 48 h. We observed increased numbers of IHC–SGN synapses after exogenous IGF-1 application. Pharmacological inhibition of the IGF-1 receptor attenuated the restoration of IHC–SGN synapses by exogenous IGF-1. These findings indicated that IGF-1 induces regeneration of IHC–SGN synapses in cochlear explant cultures from postnatal day 2 mice. Therefore, in a future study we will perform in vivo experiments using adult mice to ascertain the effects of IGF-1 on the regeneration of IHC–SGN synapses.

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Progressive Hearing Damage after Exposure to Repeated Low-Intensity Blasts in Chinchillas

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Tao Chen, Kyle Smith, Shangyuan Jiang, Tianyu Zhang, Rong Z. Gan

Abstract

Hearing damage caused by blast waves is a frequent and common injury for Service members. However, most studies have focused on high-intensity blast exposures that are known to cause moderate to severe traumatic brain injury (TBI), and fewer studies have investigated the progressive hearing damage caused by low-intensity blast exposures (below mild TBI). In this paper, we report our recent study in chinchillas to investigate the auditory function changes over the time course after repetitive exposures to low-intensity blast. Two groups of chinchillas (N=7 each) were used in this study. Group 1 was for an acute study with 2 blasts and Group 2 for progressive study with 3 blasts on Day 1 and observed for 7 days. Animals in both groups were exposed to blast overpressures of 21-35 kPa (3-5 psi or 180-185 dB SPL) at which the eardrum was usually not ruptured. One ear was left open while another ear was protected with an earplug. Blast overpressures were monitored at the entrance of the ear canal (P0) and near the eardrum in the canal (P1). Auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and middle latency responses (MLRs) were measured after each blast series in the acute group and on Days 1, 4, and 7 in the progressive group. Results show that hearing damage was induced in both ears after blast exposure on Day 1 and more damage was observed in open ears than plugged ears. Seven days after the three-blast series, the ABR threshold in open ears was still 7-20 dB higher on average than prior to the blasts. The MLR wave amplitude shifts were observed in both open and protected ears, which indicated central auditory damage. With the protection of an earplug, hearing thresholds had recovered to the pre-blast level by Day 7. Using this chinchilla blast model, acute and progressive hearing damages were quantified in both open and protected ears following repeated low-intensity blast exposures.

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Gap-induced inhibition of the post-auricular muscle response in humans and guinea pigs

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Caroline A. Wilson, Joel I. Berger, Jessica de Boer, Magdalena Sereda, Alan R. Palmer, Deborah A. Hall, Mark N. Wallace

Abstract

A common method for measuring changes in temporal processing sensitivity in both humans and animals makes use of GaP-induced Inhibition of the Acoustic Startle (GPIAS). It is also the basis of a common method for detecting tinnitus in rodents. However, the link to tinnitus has not been properly established because GPIAS has not yet been used to objectively demonstrate tinnitus in humans. In guinea pigs, the Preyer (ear flick) myogenic reflex is an established method for measuring the acoustic startle for the GPIAS test, while in humans, it is the eye-blink reflex. Yet, humans have a vestigial remnant of the Preyer reflex, which can be detected by measuring skin surface potentials associated with the Post-Auricular Muscle Response (PAMR). A similar electrical potential can be measured in guinea pigs and we aimed to show that the PAMR could be used to demonstrate GPIAS in both species.

In guinea pigs, we compare the GPIAS measured using the pinna movement of the Preyer reflex and the electrical potential of the PAMR to demonstrate that the two are at least equivalent. In humans, we establish for the first time that the PAMR provides a reliable way of measuring GPIAS that is a pure acoustic alternative to the multimodal eye-blink reflex. Further exploratory tests showed that while eye gaze position influenced the size of the PAMR response, it did not change the degree of GPIAS.

Our findings confirm that the PAMR is a sensitive method for measuring GPIAS and suggest that it may allow direct comparison of temporal processing between humans and animals and may provide a basis for an objective test of tinnitus.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Dijjzz

Insulin-like growth factor 1 promotes cochlear synapse regeneration after excitotoxic trauma in vitro

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Kohei Yamahara, Nakarin Asaka, Tomoko Kita, Ippei Kishimoto, Mami Matsunaga, Norio Yamamoto, Koichi Omori, Takayuki Nakagawa

Abstract

In the context of acquired sensorineural hearing loss (SNHL), cochlear hair cells have long been thought to be among the most vulnerable elements in mammalian cochleae. However, recent studies have indicated that the synaptic connection between inner hair cells (IHC) and spiral ganglion neurons (SGN) can be an important target for the treatment of SNHL. Our previous studies in patients with sudden SNHL demonstrated delayed and gradual hearing recovery following topical application of insulin-like growth factor 1 (IGF-1), suggesting that not only protective but also regenerative mechanisms may account for hearing recovery after treatment with IGF-1. We then hypothesized that IGF-1 has the potential to drive the regeneration of IHC–SGN synapses. To test this hypothesis, we investigated the effects of IGF-1 on IHC–SGN synapses using cochlear explant cultures from postnatal day 2 mice that had been damaged by exposure to the excitatory amino acids N-methyl-d-aspartate and kainate. Cochlear explants that lost IHC–SGN synapses upon exposure to excitatory amino acids were cultured with exogenous IGF-1 for an additional 48 h. We observed increased numbers of IHC–SGN synapses after exogenous IGF-1 application. Pharmacological inhibition of the IGF-1 receptor attenuated the restoration of IHC–SGN synapses by exogenous IGF-1. These findings indicated that IGF-1 induces regeneration of IHC–SGN synapses in cochlear explant cultures from postnatal day 2 mice. Therefore, in a future study we will perform in vivo experiments using adult mice to ascertain the effects of IGF-1 on the regeneration of IHC–SGN synapses.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2DiJYvS

Progressive Hearing Damage after Exposure to Repeated Low-Intensity Blasts in Chinchillas

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Tao Chen, Kyle Smith, Shangyuan Jiang, Tianyu Zhang, Rong Z. Gan

Abstract

Hearing damage caused by blast waves is a frequent and common injury for Service members. However, most studies have focused on high-intensity blast exposures that are known to cause moderate to severe traumatic brain injury (TBI), and fewer studies have investigated the progressive hearing damage caused by low-intensity blast exposures (below mild TBI). In this paper, we report our recent study in chinchillas to investigate the auditory function changes over the time course after repetitive exposures to low-intensity blast. Two groups of chinchillas (N=7 each) were used in this study. Group 1 was for an acute study with 2 blasts and Group 2 for progressive study with 3 blasts on Day 1 and observed for 7 days. Animals in both groups were exposed to blast overpressures of 21-35 kPa (3-5 psi or 180-185 dB SPL) at which the eardrum was usually not ruptured. One ear was left open while another ear was protected with an earplug. Blast overpressures were monitored at the entrance of the ear canal (P0) and near the eardrum in the canal (P1). Auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and middle latency responses (MLRs) were measured after each blast series in the acute group and on Days 1, 4, and 7 in the progressive group. Results show that hearing damage was induced in both ears after blast exposure on Day 1 and more damage was observed in open ears than plugged ears. Seven days after the three-blast series, the ABR threshold in open ears was still 7-20 dB higher on average than prior to the blasts. The MLR wave amplitude shifts were observed in both open and protected ears, which indicated central auditory damage. With the protection of an earplug, hearing thresholds had recovered to the pre-blast level by Day 7. Using this chinchilla blast model, acute and progressive hearing damages were quantified in both open and protected ears following repeated low-intensity blast exposures.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2U0l7Ts

Gap-induced inhibition of the post-auricular muscle response in humans and guinea pigs

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Caroline A. Wilson, Joel I. Berger, Jessica de Boer, Magdalena Sereda, Alan R. Palmer, Deborah A. Hall, Mark N. Wallace

Abstract

A common method for measuring changes in temporal processing sensitivity in both humans and animals makes use of GaP-induced Inhibition of the Acoustic Startle (GPIAS). It is also the basis of a common method for detecting tinnitus in rodents. However, the link to tinnitus has not been properly established because GPIAS has not yet been used to objectively demonstrate tinnitus in humans. In guinea pigs, the Preyer (ear flick) myogenic reflex is an established method for measuring the acoustic startle for the GPIAS test, while in humans, it is the eye-blink reflex. Yet, humans have a vestigial remnant of the Preyer reflex, which can be detected by measuring skin surface potentials associated with the Post-Auricular Muscle Response (PAMR). A similar electrical potential can be measured in guinea pigs and we aimed to show that the PAMR could be used to demonstrate GPIAS in both species.

In guinea pigs, we compare the GPIAS measured using the pinna movement of the Preyer reflex and the electrical potential of the PAMR to demonstrate that the two are at least equivalent. In humans, we establish for the first time that the PAMR provides a reliable way of measuring GPIAS that is a pure acoustic alternative to the multimodal eye-blink reflex. Further exploratory tests showed that while eye gaze position influenced the size of the PAMR response, it did not change the degree of GPIAS.

Our findings confirm that the PAMR is a sensitive method for measuring GPIAS and suggest that it may allow direct comparison of temporal processing between humans and animals and may provide a basis for an objective test of tinnitus.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Dijjzz

Dynamics of blood brain barrier permeability and tissue microstructure following controlled cortical impact injury in rat: A dynamic contrast-enhanced magnetic resonance imaging and diffusion kurtosis imaging study

Publication date: Available online 17 January 2019

Source: Magnetic Resonance Imaging

Author(s): Mengmeng Yu, Mingliang Wang, Dianxu Yang, Xiaoer Wei, Wenbin Li

Abstract

Objective

The blood-brain barrier (BBB) and cerebral tissue microstructure can be impaired following traumatic brain injury (TBI). However, the spatiotemporal changes of BBB leakage and tissue microstructure are not completely understood. In this study, we evaluated the spatiotemporal changes of BBB leakage and tissue microstructure using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion kurtosis imaging (DKI) in controlled cortical impact (CCI) rats.

Materials and methods

The DCE-MRI parameters volume transfer coefficient (K^trans) and DKI parameters were longitudinally measured in bilateral cortex, hippocampus, thalamus and corpus callosum (CC) at baseline (D0), acute stage (D1, D3), and subacute stage (D7, D14 and D28) post-injury. Immunohistochemistry analysis was performed at D28 after MRI scanning. Repeated-measures ANOVA was used to assess the temporal changes of MRI parameters.

Results

K^trans abnormality was only localized to ipsilateral perilesional cortex with a significant temporal change (F = 144.2, p < 0.0001). Compared to baseline, increased mean kurtosis (MK) was observed in ipsilateral regions of cortex and hippocampus and CC for all the time points (p < 0.05 for all). Increased MK was also observed in ipsilateral thalamus (p = 0.005) at subacute stage but not at acute stage while no change was observed with MD and FA (p > 0.05 for both). In ipsilateral cortex, the overall K^trans value of D0, D1, D3, D7, D14, and D28 post-injury were significantly correlated with MK value (r = 0.84, p < 0.0001). The CCI group showed higher staining of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) and lower staining of neuron-specific nuclear protein (NeuN) and myelin basic protein (MBP) in ipsilateral regions of cortex, hippocampus, thalamus and CC (p < 0.05 for all) as compared to control group. There were no significant differences in the contralateral regions by immunohistochemistry.

Conclusion

The BBB disruption reflected by K^trans correlated well with MK value in ipsilateral cortex. In addition, MK could detect the delayed microstructural changes in thalamus. DCE-MRI and DKI could be used to assess the BBB breakdown and cerebral microstructural changes of TBI.

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Dynamics of blood brain barrier permeability and tissue microstructure following controlled cortical impact injury in rat: A dynamic contrast-enhanced magnetic resonance imaging and diffusion kurtosis imaging study

Publication date: Available online 17 January 2019

Source: Magnetic Resonance Imaging

Author(s): Mengmeng Yu, Mingliang Wang, Dianxu Yang, Xiaoer Wei, Wenbin Li

Abstract

Objective

The blood-brain barrier (BBB) and cerebral tissue microstructure can be impaired following traumatic brain injury (TBI). However, the spatiotemporal changes of BBB leakage and tissue microstructure are not completely understood. In this study, we evaluated the spatiotemporal changes of BBB leakage and tissue microstructure using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion kurtosis imaging (DKI) in controlled cortical impact (CCI) rats.

Materials and methods

The DCE-MRI parameters volume transfer coefficient (K^trans) and DKI parameters were longitudinally measured in bilateral cortex, hippocampus, thalamus and corpus callosum (CC) at baseline (D0), acute stage (D1, D3), and subacute stage (D7, D14 and D28) post-injury. Immunohistochemistry analysis was performed at D28 after MRI scanning. Repeated-measures ANOVA was used to assess the temporal changes of MRI parameters.

Results

K^trans abnormality was only localized to ipsilateral perilesional cortex with a significant temporal change (F = 144.2, p < 0.0001). Compared to baseline, increased mean kurtosis (MK) was observed in ipsilateral regions of cortex and hippocampus and CC for all the time points (p < 0.05 for all). Increased MK was also observed in ipsilateral thalamus (p = 0.005) at subacute stage but not at acute stage while no change was observed with MD and FA (p > 0.05 for both). In ipsilateral cortex, the overall K^trans value of D0, D1, D3, D7, D14, and D28 post-injury were significantly correlated with MK value (r = 0.84, p < 0.0001). The CCI group showed higher staining of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) and lower staining of neuron-specific nuclear protein (NeuN) and myelin basic protein (MBP) in ipsilateral regions of cortex, hippocampus, thalamus and CC (p < 0.05 for all) as compared to control group. There were no significant differences in the contralateral regions by immunohistochemistry.

Conclusion

The BBB disruption reflected by K^trans correlated well with MK value in ipsilateral cortex. In addition, MK could detect the delayed microstructural changes in thalamus. DCE-MRI and DKI could be used to assess the BBB breakdown and cerebral microstructural changes of TBI.

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Detection of Intra-Articular Screw Penetration of Proximal Humerus Fractures: Is Postoperative Computed Tomography the Necessary Imaging Modality?

Publication date: February 2019

Source: Academic Radiology, Volume 26, Issue 2

Author(s): Xiaoyang Jia, Yanxi Chen, Minfei Qiang, Kun Zhang, Haobo Li, Yuchen Jiang, Yijie Zhang

Rationale and Objective

Screw penetration is the common complication of proximal humerus fractures treated with locking plates. This study compared postoperative plain radiography to computed tomography (CT) for their abilities in determining screw penetration, and was to evaluate whether advanced imaging modalities (two-dimensional [2D] CT; three-dimensional [3D] CT) could increase surgeons' level of confidence regarding their diagnoses.

Materials and Methods

Two observers reviewed radiological images of 134 patients who sustained proximal humerus fractures treated with locking plates. The observers were asked to answer two questions: (1) Is there screw penetrating into glenohumeral joint for this patient (Yes/No)? and (2) On a scale from 0 to 10, how confident are you about this diagnosis: (0–10) (0 = not at all confident; 10 = very confident)? Three evaluations were performed: (1) plain radiography alone, (2) radiography and 2D CT 4 weeks later, and (3) radiography in combination with 2D and 3D CT after that. This process was then repeated for intraobserver analysis.

Results

CT obtained almost perfect interobserver and intraobserver agreement (0.818–0.961), which was higher than radiography (0.377–0.655). For incidence of screw penetration, the significant difference was found between radiographs and CT images (P < .0125), but not between 2D and 3D CT images (P > .05). For confidence of diagnosis, the differences between imaging modalities were significant (all P < .001).

Conclusions

We suggest that postoperative CT scans (especially 3D CT images) should be used to evaluate the intra-articular screw penetration of proximal humerus fractures, especially when surgeons have not enough confidence in determining screw penetration using radiography alone.

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Breast Cancer Molecular Subtype Prediction by Mammographic Radiomic Features

Publication date: February 2019

Source: Academic Radiology, Volume 26, Issue 2

Author(s): Wenjuan Ma, Yumei Zhao, Yu Ji, Xinpeng Guo, Xiqi Jian, Peifang Liu, Shandong Wu

Rationale and Objectives

This study aimed to investigate whether quantitative radiomic features extracted from digital mammogram images are associated with molecular subtypes of breast cancer.

Materials and Methods

In this institutional review board–approved retrospective study, we collected 331 Chinese women who were diagnosed with invasive breast cancer in 2015. This cohort included 29 triple-negative, 45 human epidermal growth factor receptor 2 (HER2)-enriched, 36 luminal A, and 221 luminal B lesions. A set of 39 quantitative radiomic features, including morphologic, grayscale statistic, and texture features, were extracted from the segmented lesion area. Three binary classifications of the subtypes were performed: triple-negative vs non–triple-negative, HER2-enriched vs non–HER2-enriched, and luminal (A + B) vs nonluminal. The Naive Bayes machine learning scheme was employed for the classification, and the least absolute shrink age and selection operator method was used to select the most predictive features for the classifiers. Classification performance was evaluated by the area under receiver operating characteristic curve and accuracy.

Results

The model that used the combination of both the craniocaudal and the mediolateral oblique view images achieved the overall best performance than using either of the two views alone, yielding an area under receiver operating characteristic curve (or accuracy) of 0.865 (0.796) for triple-negative vs non–triple-negative, 0.784 (0.748) for HER2-enriched vs non–HER2-enriched, and 0.752 (0.788) for luminal vs nonluminal subtypes. Twelve most predictive features were selected by the least absolute shrink age and selection operator method and four of them (ie, roundness, concavity, gray mean, and correlation) showed a statistical significance (P < .05) in the subtype classification.

Conclusions

Our study showed that quantitative radiomic imaging features of breast tumor extracted from digital mammograms are associated with breast cancer subtypes. Future larger studies are needed to further evaluate the findings.

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Machine Learning to Differentiate T2-Weighted Hyperintense Uterine Leiomyomas from Uterine Sarcomas by Utilizing Multiparametric Magnetic Resonance Quantitative Imaging Features

Publication date: Available online 17 January 2019

Source: Academic Radiology

Author(s): Masataka Nakagawa, Takeshi Nakaura, Tomohiro Namimoto, Yuji Iyama, Masafumi Kidoh, Kenichiro Hirata, Yasunori Nagayama, Hideaki Yuki, Seitaro Oda, Daisuke Utsunomiya, Yasuyuki Yamashita

Rationale and Objective

Uterine leiomyomas with high signal intensity on T2-weighted imaging (T2WI) can be difficult to distinguish from sarcomas. This study assessed the feasibility of using machine learning to differentiate uterine sarcomas from leiomyomas with high signal intensity on T2WI on multiparametric magnetic resonance imaging.

Materials and Methods

This retrospective study included 80 patients (50 with benign leiomyoma and 30 with uterine sarcoma) who underwent pelvic 3 T magnetic resonance imaging examination for the evaluation of uterine myometrial smooth muscle masses with high signal intensity on T2WI. We used six machine learning techniques to develop prediction models based on 12 texture parameters on T1WI and T2WI, apparent diffusion coefficient maps, and contrast-enhanced T1WI, as well as tumor size and age. We calculated the areas under the curve (AUCs) using receiver-operating characteristic analysis for each model by 10-fold cross-validation and compared these to those for two board-certified radiologists.

Results

The eXtreme Gradient Boosting model gave the highest AUC (0.93), followed by the random forest, support vector machine, multilayer perceptron, k-nearest neighbors, and logistic regression models. Age was the most important factor for differentiation (leiomyoma 44.9 ± 11.1 years; sarcoma 58.9 ± 14.7 years; p < 0.001). The AUC for the eXtreme Gradient Boosting was significantly higher than those for both radiologists (0.93 vs 0.80 and 0.68, p = 0.03 and p < 0.001, respectively).

Conclusion

Machine learning outperformed experienced radiologists in the differentiation of uterine sarcomas from leiomyomas with high signal intensity on T2WI.

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The Importance of Learning to Listen

Publication date: Available online 17 January 2019

Source: Academic Radiology

Author(s): Richard B. Gunderman

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Detection of Intra-Articular Screw Penetration of Proximal Humerus Fractures: Is Postoperative Computed Tomography the Necessary Imaging Modality?

Publication date: February 2019

Source: Academic Radiology, Volume 26, Issue 2

Author(s): Xiaoyang Jia, Yanxi Chen, Minfei Qiang, Kun Zhang, Haobo Li, Yuchen Jiang, Yijie Zhang

Rationale and Objective

Screw penetration is the common complication of proximal humerus fractures treated with locking plates. This study compared postoperative plain radiography to computed tomography (CT) for their abilities in determining screw penetration, and was to evaluate whether advanced imaging modalities (two-dimensional [2D] CT; three-dimensional [3D] CT) could increase surgeons' level of confidence regarding their diagnoses.

Materials and Methods

Two observers reviewed radiological images of 134 patients who sustained proximal humerus fractures treated with locking plates. The observers were asked to answer two questions: (1) Is there screw penetrating into glenohumeral joint for this patient (Yes/No)? and (2) On a scale from 0 to 10, how confident are you about this diagnosis: (0–10) (0 = not at all confident; 10 = very confident)? Three evaluations were performed: (1) plain radiography alone, (2) radiography and 2D CT 4 weeks later, and (3) radiography in combination with 2D and 3D CT after that. This process was then repeated for intraobserver analysis.

Results

CT obtained almost perfect interobserver and intraobserver agreement (0.818–0.961), which was higher than radiography (0.377–0.655). For incidence of screw penetration, the significant difference was found between radiographs and CT images (P < .0125), but not between 2D and 3D CT images (P > .05). For confidence of diagnosis, the differences between imaging modalities were significant (all P < .001).

Conclusions

We suggest that postoperative CT scans (especially 3D CT images) should be used to evaluate the intra-articular screw penetration of proximal humerus fractures, especially when surgeons have not enough confidence in determining screw penetration using radiography alone.

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Breast Cancer Molecular Subtype Prediction by Mammographic Radiomic Features

Publication date: February 2019

Source: Academic Radiology, Volume 26, Issue 2

Author(s): Wenjuan Ma, Yumei Zhao, Yu Ji, Xinpeng Guo, Xiqi Jian, Peifang Liu, Shandong Wu

Rationale and Objectives

This study aimed to investigate whether quantitative radiomic features extracted from digital mammogram images are associated with molecular subtypes of breast cancer.

Materials and Methods

In this institutional review board–approved retrospective study, we collected 331 Chinese women who were diagnosed with invasive breast cancer in 2015. This cohort included 29 triple-negative, 45 human epidermal growth factor receptor 2 (HER2)-enriched, 36 luminal A, and 221 luminal B lesions. A set of 39 quantitative radiomic features, including morphologic, grayscale statistic, and texture features, were extracted from the segmented lesion area. Three binary classifications of the subtypes were performed: triple-negative vs non–triple-negative, HER2-enriched vs non–HER2-enriched, and luminal (A + B) vs nonluminal. The Naive Bayes machine learning scheme was employed for the classification, and the least absolute shrink age and selection operator method was used to select the most predictive features for the classifiers. Classification performance was evaluated by the area under receiver operating characteristic curve and accuracy.

Results

The model that used the combination of both the craniocaudal and the mediolateral oblique view images achieved the overall best performance than using either of the two views alone, yielding an area under receiver operating characteristic curve (or accuracy) of 0.865 (0.796) for triple-negative vs non–triple-negative, 0.784 (0.748) for HER2-enriched vs non–HER2-enriched, and 0.752 (0.788) for luminal vs nonluminal subtypes. Twelve most predictive features were selected by the least absolute shrink age and selection operator method and four of them (ie, roundness, concavity, gray mean, and correlation) showed a statistical significance (P < .05) in the subtype classification.

Conclusions

Our study showed that quantitative radiomic imaging features of breast tumor extracted from digital mammograms are associated with breast cancer subtypes. Future larger studies are needed to further evaluate the findings.

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Institutional Implementation of a Structured Reporting System: Our Experience with the Brain Tumor Reporting and Data System

Publication date: Available online 18 January 2019

Source: Academic Radiology

Author(s): Ashwani Gore, Michael J. Hoch, Hui-Kuo G. Shu, Jeffrey J. Olson, Alfredo D. Voloschin, Brent D. Weinberg

Rationale and Objectives

Analyze the impact of implementing a structured reporting system for primary brain tumors, the Brain Tumor Reporting and Data System, on attitudes toward radiology reports at a single institution.

Materials and Methods

Following Institutional Review Board approval, an initial 22 question, 5 point (1—worst to 5—best), survey was sent to faculty members, house staff members, and nonphysician providers at our institution who participate in the direct care of brain tumor patients. Results were used to develop a structured reporting strategy for brain tumors which was implemented across an entire neuroradiology section in a staged approach. Nine months following structured reporting implementation, a follow-up 27 question survey was sent to the same group of providers. Keyword search of radiology reports was used to assess usage of Brain Tumor Reporting and Data System over time.

Results

Fifty-three brain tumor care providers responded to the initial survey and 38 to the follow-up survey. After implementing BT-RADS, respondents reported improved attitudes across multiple areas including: report consistency (4.3 vs. 3.4; p < 0.001), report ambiguity (4.2 vs. 3.2, p < 0.001), radiologist/physician communication (4.5 vs. 3.8; p < 0.001), facilitation of patient management (4.2 vs. 3.6; p = 0.003), and confidence in reports (4.3 vs. 3.5; p < 0.001). Providers were more satisfied with the BT-RADS structured reporting system (4.3 vs. 3.7; p = 0.04). Use of the reporting template progressively increased with 81% of brain tumor reports dictated using the new template by 9 months.

Conclusion

Implementing a structured template for brain tumor imaging improves perception of radiology reports among radiologists and referring providers involved in the care of brain tumor patients.

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Does the Apparent Diffusion Coefficient Value Predict Permanent Cerebral Ischemia/Reperfusion Injury in Rats?

Publication date: Available online 17 January 2019

Source: Academic Radiology

Author(s): Jae-Im Kwon, Chul-Woong Woo, Kyung-Won Kim, Yoonseok Choi, Sang-Tae Kim, Yun Jae Kim, Jeeheon Kang, Do-Wan Lee, Eunyoung Tak, Jeong-Kon Kim, Seung-Chae Jung, Tae-Hyung Kim, Dong-Cheol Woo

Rationale and Objectives

Variation in tissue damage after cerebral ischemia/reperfusion (I/R) can cause uncertainty in stroke-related studies, which can be reduced if the damage can be predicted early after ischemia by measuring the apparent diffusion coefficient (ADC). We investigated whether ADC measurement in the acute phase can predict permanent cerebral I/R injury.

Materials and Methods

The middle cerebral artery occlusion model was established using the intraluminal suture method to induce 60 minutes of ischemia followed by reperfusion in rats. T2-weighted images and diffusion-weighted images were obtained at 30 minutes and 24 hours after ischemia. Neuronal cell survival was assessed by neuronal nuclei (NeuN) immunofluorescence staining. The correlation between relative ADC (rADC) values at 30 minutes and I/R injury at 24 hours after ischemia was analyzed. Magnetic resonance imaging results were confirmed by histologic analysis.

Results

The correlation between rADC values at 30 minutes and 24 hours was strong in the ischemic core and peri-infarct region but moderate in the anterior choroidal and hypothalamic region. Histologic analysis revealed that the correlation between rADC values at 30 minutes and the number of NeuN-positive cells at 24 hours was strong in the ischemic core and peri-infarct region but moderate in the anterior choroidal and hypothalamic region. Furthermore, there was a strong positive correlation between the sum of rADC values of three regions at 30 minutes and the infarct volume at 24 hours.

Conclusion

ADC measurement in the acute phase can predict permanent cerebral I/R injury and provide important information for the evaluation of ischemic stroke.

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The Importance of Learning to Listen

Publication date: Available online 17 January 2019

Source: Academic Radiology

Author(s): Richard B. Gunderman

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Dermatomyositis associated with omalizumab therapy for severe asthma: a case report

Omalizumab is a humanized monoclonal antibody widely used for treatment of persistent allergic asthma and antihistamine-refractory chronic urticaria. Immediate adverse events to omalizumab are well characteriz...

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Dermatomyositis associated with omalizumab therapy for severe asthma: a case report

Omalizumab is a humanized monoclonal antibody widely used for treatment of persistent allergic asthma and antihistamine-refractory chronic urticaria. Immediate adverse events to omalizumab are well characteriz...

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A retrospective study of clinical features of cough variant asthma in Chinese adults

Clinical features of cough variant asthma (CVA) in Chinese adults are largely uncertain.

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In vitro Bioactivity of Extracts from Seeds of Cassia absus L.Growing in Pakistan

Publication date: Available online 17 January 2019

Source: Journal of Herbal Medicine

Author(s): Saeed Ahmad, Ayesha Hassan, Tayyeba Rehman, Abdul Basit, Anbreen Tahir, Muhammad Adeel Arshad

Abstract

Cassia absus seeds are widely used in traditional medicine for treatment of skin infections, wound healing, hypertension, peptic ulcers and anuria. The current study evaluated the antioxidant, antibacterial, and enzyme inhibitory activity of extracts obtained from the seeds of C. absus L. (Leguminosae) to determine a mechanism for the traditional use of the seeds. Crude ethanolic extract of C.absus seeds was prepared by maceration method and n-butanol, choloroform, n-hexane and water fractions were prepared from crude ethanol extract. The antibacterial activity of samples was determined by agar well diffusion and broth micro dilution assay. The antioxidant activity of the crude extract and fractions was evaluated for free radical scavenging activity by DPPH assay. The enzyme inhibition activity of crude extract and fractions was determined against urease, carbonic anhydrase and xanthine oxidase. The n-hexane and n-butanol fractions showed promising activity against gram-positive bacteria when compared with ceftriaxone as a standard. Moreover, the crude ethanol extract and water fraction displayed the most potent activity in urease inhibition assay. The results showed that crude extract and all the fractions have urease inhibition. In the case of carbonic anhydrase, only the crude ethanolic extract and water fraction exhibited inhibitory activity. Interestingly, none of the extracts or fractions showed significant inhibitory activity against xanthine oxidase and DPPH. Data obtained tends to corroborate with the reported traditional usage of the plant, as the traditional use of C. absus seeds in skin infections and wound healing could be explained by its promising antibacterial activity. The traditional diuretic, antihypertensive effect could be due to its carbonic anhydrase inhibitory activity. Anti-ulcer effect could be due to urease and carbonic anhydrase inhibition. However, further in vivo and clinical trials are required to confirm these activities of seeds. Moreover, there may also be potential to isolate promising compounds for drug discovery.

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In vitro Bioactivity of Extracts from Seeds of Cassia absus L.Growing in Pakistan

Publication date: Available online 17 January 2019

Source: Journal of Herbal Medicine

Author(s): Saeed Ahmad, Ayesha Hassan, Tayyeba Rehman, Abdul Basit, Anbreen Tahir, Muhammad Adeel Arshad

Abstract

Cassia absus seeds are widely used in traditional medicine for treatment of skin infections, wound healing, hypertension, peptic ulcers and anuria. The current study evaluated the antioxidant, antibacterial, and enzyme inhibitory activity of extracts obtained from the seeds of C. absus L. (Leguminosae) to determine a mechanism for the traditional use of the seeds. Crude ethanolic extract of C.absus seeds was prepared by maceration method and n-butanol, choloroform, n-hexane and water fractions were prepared from crude ethanol extract. The antibacterial activity of samples was determined by agar well diffusion and broth micro dilution assay. The antioxidant activity of the crude extract and fractions was evaluated for free radical scavenging activity by DPPH assay. The enzyme inhibition activity of crude extract and fractions was determined against urease, carbonic anhydrase and xanthine oxidase. The n-hexane and n-butanol fractions showed promising activity against gram-positive bacteria when compared with ceftriaxone as a standard. Moreover, the crude ethanol extract and water fraction displayed the most potent activity in urease inhibition assay. The results showed that crude extract and all the fractions have urease inhibition. In the case of carbonic anhydrase, only the crude ethanolic extract and water fraction exhibited inhibitory activity. Interestingly, none of the extracts or fractions showed significant inhibitory activity against xanthine oxidase and DPPH. Data obtained tends to corroborate with the reported traditional usage of the plant, as the traditional use of C. absus seeds in skin infections and wound healing could be explained by its promising antibacterial activity. The traditional diuretic, antihypertensive effect could be due to its carbonic anhydrase inhibitory activity. Anti-ulcer effect could be due to urease and carbonic anhydrase inhibition. However, further in vivo and clinical trials are required to confirm these activities of seeds. Moreover, there may also be potential to isolate promising compounds for drug discovery.

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An analysis of RUC methodology for determining the RVU valuation of sinus surgery

Background

The Relative Value Scale Update Committee, commonly known as the RUC, is responsible for defining the value of Current Procedural Terminology (CPT) codes. The RUC process uses survey responses reporting operative times to determine procedure reimbursement, but it is limited by low response rates, small sample sizes, and unclear generalizability of the results. By comparing actual reported intraoperative times to the times determined by the RUC process, in this study we sought to assess the performance of RUC methodology in endoscopic sinus surgery (ESS).

Methods

The ESS CPT codes that were reassessed in 2016 using the RUC method were examined in this study. Intraoperative time data for these codes were retrospectively collected from 14 medical facilities, using time stamps in the electronic health record. These actual intraoperative times were compared with the 2016 RUC survey results.

Results

There were 143 RUC physician survey responses and 446 actual procedure times included in the final analysis. There was significant variability within the RUC survey responses (ie, unilateral anterior ethmoidectomy times varied from 5 to 90 minutes). There was also a significant difference between the RUC survey results and actual intraoperative times (p < 0.001). For example, frontal sinus surgeries showed a particularly poor correlation between actual and RUC times.

Conclusion

The RUC process may not accurately estimate or value actual intraoperative times. Real‐world intraoperative times are readily accessible and may be an alternative to survey‐based methodology in the future.

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An analysis of RUC methodology for determining the RVU valuation of sinus surgery

Background

The Relative Value Scale Update Committee, commonly known as the RUC, is responsible for defining the value of Current Procedural Terminology (CPT) codes. The RUC process uses survey responses reporting operative times to determine procedure reimbursement, but it is limited by low response rates, small sample sizes, and unclear generalizability of the results. By comparing actual reported intraoperative times to the times determined by the RUC process, in this study we sought to assess the performance of RUC methodology in endoscopic sinus surgery (ESS).

Methods

The ESS CPT codes that were reassessed in 2016 using the RUC method were examined in this study. Intraoperative time data for these codes were retrospectively collected from 14 medical facilities, using time stamps in the electronic health record. These actual intraoperative times were compared with the 2016 RUC survey results.

Results

There were 143 RUC physician survey responses and 446 actual procedure times included in the final analysis. There was significant variability within the RUC survey responses (ie, unilateral anterior ethmoidectomy times varied from 5 to 90 minutes). There was also a significant difference between the RUC survey results and actual intraoperative times (p < 0.001). For example, frontal sinus surgeries showed a particularly poor correlation between actual and RUC times.

Conclusion

The RUC process may not accurately estimate or value actual intraoperative times. Real‐world intraoperative times are readily accessible and may be an alternative to survey‐based methodology in the future.

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Age-related changes in attention control and their relationship with gait performance in older adults with high risk of falls

Publication date: Available online 18 January 2019

Source: NeuroImage

Author(s): N.B. Fernandez, M. Hars, A. Trombetti, P. Vuilleumier

Abstract

Background

Falls are the leading cause of injury-related deaths in the elderly worldwide. Both gait impairment and cognitive decline have been shown to constitute major fall risk factors. However, further investigations are required to establish a more precise link between the influence of age on brain systems mediating executive cognitive functions and their relationship with gait disturbances, and thus help define novel markers and better guide remediation strategies to prevent falls.

Methods

Event-related functional magnetic resonance imaging (fMRI) was used to evaluate age-related effects on the recruitment of executive control brain network in selective attention task, as measured with a flanker paradigm. Brain activation patterns were compared between twenty young (21 years ± 2.5) and thirty-four old participants (72 years ± 5.3) with high fall risks. We then determined to what extend age-related differences in activation patterns were associated with alterations in several gait parameters, measured with electronic devices providing a precise quantitative evaluation of gait, as well as with alterations in several aspects of cognitive and physical abilities.

Results

We found that both young and old participants recruited a distributed fronto-parietal-occipital network during interference by incongruent distractors in the flanker task. However, additional activations were observed in posterior parieto-occipital areas in the older relative to the younger participants. Furthermore, a differential recruitment of both the left dorsal parieto-occipital sulcus and precuneus was significantly correlated with higher gait variability. Besides, decreased activation in the right cerebellum was found in the older with poorer cognitive processing speed scores.

Conclusions

Overall results converge to indicate greater sensitivity to attention interference and heightened recruitment of cortical executive control systems in the elderly with fall risks. Critically, this change was associated with selective increases in gait variability indices, linking attentional control with gait performance in elderly with high risks of falls.

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Adaptive paradigms for mapping phonological regions in individual participants

Publication date: Available online 18 January 2019

Source: NeuroImage

Author(s): Melodie Yen, Andrew T. DeMarco, Stephen M. Wilson

Abstract

Phonological encoding depends on left-lateralized regions in the supramarginal gyrus and the ventral precentral gyrus. Localization of these phonological regions in individual participants—including individuals with language impairments—is important in several research and clinical contexts. To localize these regions, we developed two paradigms that load on phonological encoding: a rhyme judgment task and a syllable counting task. Both paradigms relied on an adaptive staircase design to ensure that each individual performed each task at a similarly challenging level. The goal of this study was to assess the validity and reliability of the two paradigms, in terms of their ability to consistently produce left-lateralized activations of the supramarginal gyrus and ventral precentral gyrus in neurologically normal individuals with presumptively normal language localization. Sixteen participants were scanned with fMRI as they performed the rhyme judgment paradigm, the syllable counting paradigm, and an adaptive semantic paradigm that we have described previously. We found that the rhyme and syllable paradigms both yielded left-lateralized supramarginal and ventral precentral activations in the majority of participants. The rhyme paradigm produced more lateralized and more reliable activations, and so should be favored in future applications. In contrast, the semantic paradigm did not reveal supramarginal or precentral activations in most participants, suggesting that the recruitment of these regions is indeed driven by phonological encoding, not language processing in general. In sum, the adaptive rhyme judgment paradigm was effective in localizing left-lateralized phonological encoding regions in individual participants, and, in conjunction with the adaptive semantic paradigm, can be used to map individual language networks.

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Age-related changes in attention control and their relationship with gait performance in older adults with high risk of falls

Publication date: Available online 18 January 2019

Source: NeuroImage

Author(s): N.B. Fernandez, M. Hars, A. Trombetti, P. Vuilleumier

Abstract

Background

Falls are the leading cause of injury-related deaths in the elderly worldwide. Both gait impairment and cognitive decline have been shown to constitute major fall risk factors. However, further investigations are required to establish a more precise link between the influence of age on brain systems mediating executive cognitive functions and their relationship with gait disturbances, and thus help define novel markers and better guide remediation strategies to prevent falls.

Methods

Event-related functional magnetic resonance imaging (fMRI) was used to evaluate age-related effects on the recruitment of executive control brain network in selective attention task, as measured with a flanker paradigm. Brain activation patterns were compared between twenty young (21 years ± 2.5) and thirty-four old participants (72 years ± 5.3) with high fall risks. We then determined to what extend age-related differences in activation patterns were associated with alterations in several gait parameters, measured with electronic devices providing a precise quantitative evaluation of gait, as well as with alterations in several aspects of cognitive and physical abilities.

Results

We found that both young and old participants recruited a distributed fronto-parietal-occipital network during interference by incongruent distractors in the flanker task. However, additional activations were observed in posterior parieto-occipital areas in the older relative to the younger participants. Furthermore, a differential recruitment of both the left dorsal parieto-occipital sulcus and precuneus was significantly correlated with higher gait variability. Besides, decreased activation in the right cerebellum was found in the older with poorer cognitive processing speed scores.

Conclusions

Overall results converge to indicate greater sensitivity to attention interference and heightened recruitment of cortical executive control systems in the elderly with fall risks. Critically, this change was associated with selective increases in gait variability indices, linking attentional control with gait performance in elderly with high risks of falls.

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Adaptive paradigms for mapping phonological regions in individual participants

Publication date: Available online 18 January 2019

Source: NeuroImage

Author(s): Melodie Yen, Andrew T. DeMarco, Stephen M. Wilson

Abstract

Phonological encoding depends on left-lateralized regions in the supramarginal gyrus and the ventral precentral gyrus. Localization of these phonological regions in individual participants—including individuals with language impairments—is important in several research and clinical contexts. To localize these regions, we developed two paradigms that load on phonological encoding: a rhyme judgment task and a syllable counting task. Both paradigms relied on an adaptive staircase design to ensure that each individual performed each task at a similarly challenging level. The goal of this study was to assess the validity and reliability of the two paradigms, in terms of their ability to consistently produce left-lateralized activations of the supramarginal gyrus and ventral precentral gyrus in neurologically normal individuals with presumptively normal language localization. Sixteen participants were scanned with fMRI as they performed the rhyme judgment paradigm, the syllable counting paradigm, and an adaptive semantic paradigm that we have described previously. We found that the rhyme and syllable paradigms both yielded left-lateralized supramarginal and ventral precentral activations in the majority of participants. The rhyme paradigm produced more lateralized and more reliable activations, and so should be favored in future applications. In contrast, the semantic paradigm did not reveal supramarginal or precentral activations in most participants, suggesting that the recruitment of these regions is indeed driven by phonological encoding, not language processing in general. In sum, the adaptive rhyme judgment paradigm was effective in localizing left-lateralized phonological encoding regions in individual participants, and, in conjunction with the adaptive semantic paradigm, can be used to map individual language networks.

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Exploring the Use of ECochG Testing During Electrode Insertion in Cochlear Implant Surgery

Conditions:   Cochlear Implants;   Hearing Preservation Intervention:   Procedure: Electrocochlography Sponsors:   Cambridge University Hospitals NHS Foundation Trust;   University of Cambridge Recruiting (Source: ClinicalTrials.gov)

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Clinical Study of Minimally Invasive Ponto Surgical Technique (MIPS) - Design Iteration

Conditions:   Bone Conduction Deafness;   Unilateral Deafness;   Middle Ear Deafness;   Mixed Hearing Loss Intervention:   Device: Minimally Invasive Ponto Surgery Sponsor:   Oticon Medical Recruiting (Source: ClinicalTrials.gov)

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Exploring the Use of ECochG Testing During Electrode Insertion in Cochlear Implant Surgery

Conditions:   Cochlear Implants;   Hearing Preservation Intervention:   Procedure: Electrocochlography Sponsors:   Cambridge University Hospitals NHS Foundation Trust;   University of Cambridge Recruiting (Source: ClinicalTrials.gov)

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from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2DguF6X

Clinical Study of Minimally Invasive Ponto Surgical Technique (MIPS) - Design Iteration

Conditions:   Bone Conduction Deafness;   Unilateral Deafness;   Middle Ear Deafness;   Mixed Hearing Loss Intervention:   Device: Minimally Invasive Ponto Surgery Sponsor:   Oticon Medical Recruiting (Source: ClinicalTrials.gov)

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Regional Metabolite Concentrations in Aging Human Brain: Comparison of Short-TE Whole Brain MR Spectroscopic Imaging and Single Voxel Spectroscopy at 3T

Abstract

Purpose

The aim of this study was to compare a recently established whole brain MR spectroscopic imaging (wbMRSI) technique using spin-echo planar spectroscopic imaging (EPSI) acquisition and the Metabolic Imaging and Data Analysis System (MIDAS) software package with single voxel spectroscopy (SVS) technique and LCModel analysis for determination of relative metabolite concentrations in aging human brain.

Methods

A total of 59 healthy subjects aged 20–70 years (n ≥ 5 per age decade for each gender) underwent a wbEPSI scan and 3 SVS scans of a 4 ml voxel volume located in the right basal ganglia, occipital grey matter and parietal white matter. Concentration ratios to total creatine (tCr) for N‑acetylaspartate (NAA/tCr), total choline (tCho/tCr), glutamine (Gln/tCr), glutamate (Glu/tCr) and myoinositol (mI/tCr) were obtained both from EPSI and SVS acquisitions with either LCModel or MIDAS. In addition, an aqueous phantom containing known metabolite concentrations was also measured.

Results

Metabolite concentrations obtained with wbMRSI and SVS were comparable and consistent with those reported previously. Decreases of NAA/tCr and increases of line width with age were found with both techniques, while the results obtained from EPSI acquisition revealed generally narrower line widths and smaller Cramer-Rao lower bounds than those from SVS data.

Conclusion

The wbMRSI could be used to estimate metabolites in vivo and in vitro with the same reliability as using SVS, with the main advantage being the ability to determine metabolite concentrations in multiple brain structure simultaneously in vivo. It is expected to be widely used in clinical diagnostics and neuroscience.

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Regional Metabolite Concentrations in Aging Human Brain: Comparison of Short-TE Whole Brain MR Spectroscopic Imaging and Single Voxel Spectroscopy at 3T

Abstract

Purpose

The aim of this study was to compare a recently established whole brain MR spectroscopic imaging (wbMRSI) technique using spin-echo planar spectroscopic imaging (EPSI) acquisition and the Metabolic Imaging and Data Analysis System (MIDAS) software package with single voxel spectroscopy (SVS) technique and LCModel analysis for determination of relative metabolite concentrations in aging human brain.

Methods

A total of 59 healthy subjects aged 20–70 years (n ≥ 5 per age decade for each gender) underwent a wbEPSI scan and 3 SVS scans of a 4 ml voxel volume located in the right basal ganglia, occipital grey matter and parietal white matter. Concentration ratios to total creatine (tCr) for N‑acetylaspartate (NAA/tCr), total choline (tCho/tCr), glutamine (Gln/tCr), glutamate (Glu/tCr) and myoinositol (mI/tCr) were obtained both from EPSI and SVS acquisitions with either LCModel or MIDAS. In addition, an aqueous phantom containing known metabolite concentrations was also measured.

Results

Metabolite concentrations obtained with wbMRSI and SVS were comparable and consistent with those reported previously. Decreases of NAA/tCr and increases of line width with age were found with both techniques, while the results obtained from EPSI acquisition revealed generally narrower line widths and smaller Cramer-Rao lower bounds than those from SVS data.

Conclusion

The wbMRSI could be used to estimate metabolites in vivo and in vitro with the same reliability as using SVS, with the main advantage being the ability to determine metabolite concentrations in multiple brain structure simultaneously in vivo. It is expected to be widely used in clinical diagnostics and neuroscience.

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Protein contact dermatitis by flours in a pastry chef

Protein contact dermatitis is a chronic, recurring dermatitis triggered by type I hypersensitivity to protein allergen¹. We report a case caused by flours in a pastry chef.

This article is protected by copyright. All rights reserved.

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Methylisothiazolinone allergic contact dermatitis: assessment of relapses in 139 patients after avoidance advice

Background

Methylisothiazolinone (MI) is a preservative responsible for an epidemic of allergic contact dermatitis (ACD). Few studies have been published on the prognosis of patients with MI‐induced ACD.

Objectives

To evaluate relapses of MI‐induced ACD and difficulties in avoiding MI in patients who had received avoidance advice.

Methods

Retrospective study of patients with ACD to MI diagnosed in two specialized dermato‐allergology units between 2010 and 2015. Median follow‐up was 3 years.

Results

Relapses were observed in 64% of 139 included patients and were severe in 18%. "Rinse‐off" cosmetics were responsible for the largest proportion of relapses (27%). Median time to relapse was 5 months. Sixty nine per cent of relapses were on the hands and 29% on the face. Risk factors for relapsing were hand eczema and personal history of atopy. The main difficulties encountered in the avoidance strategy were hidden sources of MI, the lack of labelling on industrial products, the complexity of cosmetic labelling, and remembering the name of the allergen.

Conclusion

MI‐induced ACD has a poor prognosis. Its high rate of relapse is mainly due to the difficulties of avoidance. Management needs to be improved. Specialized follow‐up in the year following diagnosis is essential to educate patients.

This article is protected by copyright. All rights reserved.

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Low amount of formaldehyde in topical medication and cosmetics: is it clinically relevant?

It is difficult for the patients allergic to formaldehyde to totally avoid contact with products containing it as its presence cannot be determined from the ingredient labelling with certainty (1). The aim of this study was to investigate whether formaldehyde could be detected in topical medicines and eye cosmetics when there was no labelled presence of formaldehyde or formaldehyde‐releasers.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2MghRQT

Short exposures and glove protection from (meth)acrylates in nail beauticians – thoughts on a rising concern

Allergic contact dermatitis (ACD) from (meth)acrylates in nail aesthetics is a rising concern, namely in the occupational setting (1)(2). Some technicians may have to abandon the job, as allergen avoidance is difficult (3). Aiming to evaluate the capacity of gloves to protect from occupational ACD we performed patch tests with glove fragments placed between the allergens and patients' skin for different time periods, in patients with occupational ACD and positive patch tests to the (meth)acrylates and negative patch tests to gloves.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2sxWCB2

Allergic contact dermatitis caused by isopropyl methylphenol, a new hapten

Isopropyl methylphenol (synonym: o‐cymen‐5‐ol, Biosol; CAS no. 3228‐02‐2) (Fig. 1) is used as anti‐mold and general anti‐microbial agent, as preservative, and as antioxidant. It is found in many pharmaceuticals, including over‐the‐counter (OTC) drugs; quasi‐drugs; and cosmetics because it non irritating to the skin and considered not to be a sensitizer¹. However, three cases of allergic contact dermatitis caused by isopropyl methylphenol were reported in Japan in the 1980s²⁾³⁾. Since then, no further cases have been reported around the world. Herein, we present three additional cases of allergic contact dermatitis caused by isopropyl methylphenol.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2MjOZqV

Cinnamon‐Induced airborne occupational allergic contact dermatitis in a baker: severe flare‐up during patch testing

Cinnamon (cassia) is a well known but rarely reported cause of occupational allergic contact dermatitis (OACD) in bakers, presenting almost exclusively with hand eczema (1‐6). There is only one reported case of airborne OACD from cinnamon in bakers (2). Herein, a rare case of cinnamon‐induced airborne OACD is presented in a baker who reacted with a severe flare‐up during patch testing.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2szz5Qo

Protein contact dermatitis by flours in a pastry chef

Protein contact dermatitis is a chronic, recurring dermatitis triggered by type I hypersensitivity to protein allergen¹. We report a case caused by flours in a pastry chef.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2MhndLQ

Methylisothiazolinone allergic contact dermatitis: assessment of relapses in 139 patients after avoidance advice

Background

Methylisothiazolinone (MI) is a preservative responsible for an epidemic of allergic contact dermatitis (ACD). Few studies have been published on the prognosis of patients with MI‐induced ACD.

Objectives

To evaluate relapses of MI‐induced ACD and difficulties in avoiding MI in patients who had received avoidance advice.

Methods

Retrospective study of patients with ACD to MI diagnosed in two specialized dermato‐allergology units between 2010 and 2015. Median follow‐up was 3 years.

Results

Relapses were observed in 64% of 139 included patients and were severe in 18%. "Rinse‐off" cosmetics were responsible for the largest proportion of relapses (27%). Median time to relapse was 5 months. Sixty nine per cent of relapses were on the hands and 29% on the face. Risk factors for relapsing were hand eczema and personal history of atopy. The main difficulties encountered in the avoidance strategy were hidden sources of MI, the lack of labelling on industrial products, the complexity of cosmetic labelling, and remembering the name of the allergen.

Conclusion

MI‐induced ACD has a poor prognosis. Its high rate of relapse is mainly due to the difficulties of avoidance. Management needs to be improved. Specialized follow‐up in the year following diagnosis is essential to educate patients.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2sBGDlr

Low amount of formaldehyde in topical medication and cosmetics: is it clinically relevant?

It is difficult for the patients allergic to formaldehyde to totally avoid contact with products containing it as its presence cannot be determined from the ingredient labelling with certainty (1). The aim of this study was to investigate whether formaldehyde could be detected in topical medicines and eye cosmetics when there was no labelled presence of formaldehyde or formaldehyde‐releasers.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2MghRQT

Short exposures and glove protection from (meth)acrylates in nail beauticians – thoughts on a rising concern

Allergic contact dermatitis (ACD) from (meth)acrylates in nail aesthetics is a rising concern, namely in the occupational setting (1)(2). Some technicians may have to abandon the job, as allergen avoidance is difficult (3). Aiming to evaluate the capacity of gloves to protect from occupational ACD we performed patch tests with glove fragments placed between the allergens and patients' skin for different time periods, in patients with occupational ACD and positive patch tests to the (meth)acrylates and negative patch tests to gloves.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2sxWCB2

Allergic contact dermatitis caused by isopropyl methylphenol, a new hapten

Isopropyl methylphenol (synonym: o‐cymen‐5‐ol, Biosol; CAS no. 3228‐02‐2) (Fig. 1) is used as anti‐mold and general anti‐microbial agent, as preservative, and as antioxidant. It is found in many pharmaceuticals, including over‐the‐counter (OTC) drugs; quasi‐drugs; and cosmetics because it non irritating to the skin and considered not to be a sensitizer¹. However, three cases of allergic contact dermatitis caused by isopropyl methylphenol were reported in Japan in the 1980s²⁾³⁾. Since then, no further cases have been reported around the world. Herein, we present three additional cases of allergic contact dermatitis caused by isopropyl methylphenol.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2MjOZqV

Cinnamon‐Induced airborne occupational allergic contact dermatitis in a baker: severe flare‐up during patch testing

Cinnamon (cassia) is a well known but rarely reported cause of occupational allergic contact dermatitis (OACD) in bakers, presenting almost exclusively with hand eczema (1‐6). There is only one reported case of airborne OACD from cinnamon in bakers (2). Herein, a rare case of cinnamon‐induced airborne OACD is presented in a baker who reacted with a severe flare‐up during patch testing.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2szz5Qo

Integration of Neural Reward Processing and Appetite‐Related Signaling in Obese Females: Evidence From Resting‐State fMRI

Background

The reward‐related regions have been considered a crucial component in the regulation of eating behavior. Furthermore, appetite‐related regions associated with reward can influence eating behaviors through altered functional activity related to food in brain areas associated with emotion, memory, sensory processing, motor function, and cognitive control.

Purpose

To investigate the key nodes in obese females of reward‐related regions and, based on key nodes, to evaluate the directionality of functional connectivity between key nodes and appetite‐related regions.

Study Type

Prospective.

Population

Twenty‐eight obese and 28 normal‐weight female controls of similar age.

Field Strength/Sequence

3.0 T MRI and echo planar imaging (EPI) sequence, 3D BRAVO sequence.

Assessment

The fMRI data preprocessing was based on the Data Processing & Analysis of Brain Imaging and Statistical Parametric Mapping 12. Degree centrality calculation was based on the GRETNA toolkit and granger causality analysis were based on the DynamicBC toolbox.

Statistical Tests: Independent two‐sample t‐tests were used to assess the differences in demographic and clinical data between two groups. Two‐sample t‐tests were conducted to test the difference in degree centrality and effective connectivity of key nodes between two groups.

Results

Compared with normal‐weight controls, obese females showed an increased degree centrality in the left ventral striatum/caudate (t = 2.96808, P < 0.05) and decreased degree centrality in right orbitofrontal cortex (OFC) (t = –3.3558, P < 0.05). The obese females showed directional effective connectivity between left ventral striatum/caudate and several regions (left inferior temporal gyrus, fusiform gyrus, postcentral gyrus, and right precentral gyrus) (P < 0.05). Directional effective connectivity was also observed between the right OFC and several regions (left middle temporal gyrus, cuneus, OFC, superior temporal gyrus, middle frontal gyrus, and right inferior parietal lobule) (P < 0.05).

Data Conclusion

The left ventral striatum/caudate and right OFC are key nodes in reward‐related regions. The key nodes with reward processing mainly enhance visual processing of information and further participate in cognitive, attention, and sensorimotor processing.

Level of Evidence 1.

Technical Efficacy Stage 4.

J. Magn. Reson. Imaging 2018.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2QTQn4h

Integration of Neural Reward Processing and Appetite‐Related Signaling in Obese Females: Evidence From Resting‐State fMRI

Background

The reward‐related regions have been considered a crucial component in the regulation of eating behavior. Furthermore, appetite‐related regions associated with reward can influence eating behaviors through altered functional activity related to food in brain areas associated with emotion, memory, sensory processing, motor function, and cognitive control.

Purpose

To investigate the key nodes in obese females of reward‐related regions and, based on key nodes, to evaluate the directionality of functional connectivity between key nodes and appetite‐related regions.

Study Type

Prospective.

Population

Twenty‐eight obese and 28 normal‐weight female controls of similar age.

Field Strength/Sequence

3.0 T MRI and echo planar imaging (EPI) sequence, 3D BRAVO sequence.

Assessment

The fMRI data preprocessing was based on the Data Processing & Analysis of Brain Imaging and Statistical Parametric Mapping 12. Degree centrality calculation was based on the GRETNA toolkit and granger causality analysis were based on the DynamicBC toolbox.

Statistical Tests: Independent two‐sample t‐tests were used to assess the differences in demographic and clinical data between two groups. Two‐sample t‐tests were conducted to test the difference in degree centrality and effective connectivity of key nodes between two groups.

Results

Compared with normal‐weight controls, obese females showed an increased degree centrality in the left ventral striatum/caudate (t = 2.96808, P < 0.05) and decreased degree centrality in right orbitofrontal cortex (OFC) (t = –3.3558, P < 0.05). The obese females showed directional effective connectivity between left ventral striatum/caudate and several regions (left inferior temporal gyrus, fusiform gyrus, postcentral gyrus, and right precentral gyrus) (P < 0.05). Directional effective connectivity was also observed between the right OFC and several regions (left middle temporal gyrus, cuneus, OFC, superior temporal gyrus, middle frontal gyrus, and right inferior parietal lobule) (P < 0.05).

Data Conclusion

The left ventral striatum/caudate and right OFC are key nodes in reward‐related regions. The key nodes with reward processing mainly enhance visual processing of information and further participate in cognitive, attention, and sensorimotor processing.

Level of Evidence 1.

Technical Efficacy Stage 4.

J. Magn. Reson. Imaging 2018.

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Allergen challenge increases capsaicin evoked cough responses in allergic asthma

Changes in airway calibre and inflammation after allergen challenge in mild atopic asthmatics is associated with increased cough responses to inhaled capsaicin and spontaneous 24-hour coughing, implying neuronal sensitisation. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2W3xL5Y

Vitamin D is no substitute for the sun

(Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2QXmOiy

Challenges in Assessing the Efficacy of Systemic Corticosteroids for Severe Wheezing Episodes in Preschool Children

This letter addresses the controversial issue of the use of oral corticosteroids during wheezing exacerbations in preschool-aged children by demonstrating findings of a prematurely terminated multi-center clinical trial, discussing lessons learned, and suggesting future directions. (Source: Journal of Allergy and Clinical Immunology)

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One step forward, two steps back: The enigma of preschool wheeze

(Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2QXLWp6

Hypoxia Enhances CD8+ Tc2 Dependent Airway Hyperresponsiveness and Inflammation Through Hypoxia Inducible Factor 1 α

Hypoxia exposure amplifies CD8+ Tc2 differentiation with increased release of IL-13 in vitro and augmentation of lung allergic responses in vivo. The increases in Tc2 differentiation under hypoxia were shown to be dependent on HIF-1 α. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2QWzWEg

Hematopoietic stem cell transplantation for CD40 ligand deficiency: results from an EBMT/ESID-IEWP-SCETIDE-PIDTC Study

This manuscript reports the results of a worldwide survey of HSCT outcome in a large cohort of patients with CD40L deficiency. Key findings about survival and cure rate will be relevant to improve patients ' management. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2W1ifr7

Gamma tocopherol effect on LPS-induced sputum neutrophilia is not modified by BMI or GSTM1 genotype

Gamma tocopherol may be beneficial as a primary or complementary therapeutic agent in conditions with neutrophilic airway inflammation. Its effects are not modified by BMI or GSTM1 genotype, allowing for its use in a broader population. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2QW0RQX

Allergen challenge increases capsaicin evoked cough responses in allergic asthma

Changes in airway calibre and inflammation after allergen challenge in mild atopic asthmatics is associated with increased cough responses to inhaled capsaicin and spontaneous 24-hour coughing, implying neuronal sensitisation. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2W3xL5Y

Vitamin D is no substitute for the sun

(Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2QXmOiy

One step forward, two steps back: The enigma of preschool wheeze

(Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2QXLWp6

Double-strand break repair through homologous recombination in autosomal recessive BCL10 deficiency

DNA double-strand break (DSB) repair through homologous recombination from BCL10-/- patient is impaired. Given the relevance of DBS in the onset of cancer, it is important to highlight homologous recombination is BCL10-dependent in human fibroblasts. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2W2T0o7

Hypoxia Enhances CD8+ Tc2 Dependent Airway Hyperresponsiveness and Inflammation Through Hypoxia Inducible Factor 1 α

Hypoxia exposure amplifies CD8+ Tc2 differentiation with increased release of IL-13 in vitro and augmentation of lung allergic responses in vivo. The increases in Tc2 differentiation under hypoxia were shown to be dependent on HIF-1 α. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2QWzWEg

Hematopoietic stem cell transplantation for CD40 ligand deficiency: results from an EBMT/ESID-IEWP-SCETIDE-PIDTC Study

This manuscript reports the results of a worldwide survey of HSCT outcome in a large cohort of patients with CD40L deficiency. Key findings about survival and cure rate will be relevant to improve patients ' management. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2W1ifr7

Gamma tocopherol effect on LPS-induced sputum neutrophilia is not modified by BMI or GSTM1 genotype

Gamma tocopherol may be beneficial as a primary or complementary therapeutic agent in conditions with neutrophilic airway inflammation. Its effects are not modified by BMI or GSTM1 genotype, allowing for its use in a broader population. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2QW0RQX

B cells, CMV, and stem cell transplant

(Source: ScienceNOW)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FI52hd

Serotherapy treats a transplant hurdle

(Source: ScienceNOW)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FzRS6O

Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation

Cytomegalovirus infection is a frequent and life-threatening complication that significantly limits positive transplantation outcomes. We developed preclinical mouse models of cytomegalovirus reactivation after transplantation and found that humoral immunity is essential for preventing viral recrudescence. Preexisting antiviral antibodies decreased after transplant in the presence of graft-versus-host disease and were not replaced, owing to poor reconstitution of donor B cells and elimination of recipient plasma cells. Viral reactivation was prevented by the transfer of immune serum, without a need to identify and target specific antigenic determinants. Notably, serotherapy afforded complete protection, provided that the serum was matched to the infecting viral strain. Thus, we define the ...

MedWorm Message: Have you tried our new medical search engine? More powerful than before. Log on with your social media account. 100% free.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FHWJSl

B cells, CMV, and stem cell transplant

(Source: ScienceNOW)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FI52hd

Serotherapy treats a transplant hurdle

(Source: ScienceNOW)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FzRS6O

Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation

Cytomegalovirus infection is a frequent and life-threatening complication that significantly limits positive transplantation outcomes. We developed preclinical mouse models of cytomegalovirus reactivation after transplantation and found that humoral immunity is essential for preventing viral recrudescence. Preexisting antiviral antibodies decreased after transplant in the presence of graft-versus-host disease and were not replaced, owing to poor reconstitution of donor B cells and elimination of recipient plasma cells. Viral reactivation was prevented by the transfer of immune serum, without a need to identify and target specific antigenic determinants. Notably, serotherapy afforded complete protection, provided that the serum was matched to the infecting viral strain. Thus, we define the ...

MedWorm Message: Have you tried our new medical search engine? More powerful than before. Log on with your social media account. 100% free.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FHWJSl