Detection of increased intracerebral lactate in a mouse model of Leigh syndrome using proton MR spectroscopy

Publication date: Available online 19 January 2019

Source: Magnetic Resonance Imaging

Author(s): Yusuke Takahashi, Hidetaka Kioka, Yasunori Shintani, Akiko Ohki, Seiji Takashima, Yasushi Sakata, Takahiro Higuchi, Shigeyoshi Saito

Abstract

Purpose

To establish a brain proton magnetic resonance spectroscopy (¹H MRS) experimental system using a mouse model of Leigh syndrome for monitoring intracerebral lactate levels as a biomarker of mitochondrial disease progression.

Materials and methods

Brain ¹H MRS was performed in the Ndufs4 homozygous knockout (KO) mice, a mouse model of Leigh syndrome, and control mice on a horizontal 7.0-T magnetic resonance imaging system at age 5–9 weeks. In a subset of KO mice, survival analysis was performed according to the median of the intracerebral lactate levels. In addition, in KO mice alive until 9 weeks of age, both ¹H MRS and T₂-weighted imaging (T₂WI) were longitudinally performed in the same individuals at 5, 7, and 9 weeks of age.

Results

Brain ¹H MRS demonstrated increased lactate levels in KO mice compared with control mice (6.4 ± 1.2 mM vs. 3.3 ± 0.8 mM, p < 0.0001). The increased intracerebral lactate levels were already observed at 5 weeks of age, while no obvious abnormal findings were detected in T₂WI. Notably, an increased lactate level of >5.94 mM at week 5 was associated with a poor prognosis (median survival days: 24.5 vs. 42 days, log-rank p = 0.03). Longitudinal ¹H MRS experiments revealed temporal increase of intracerebral lactate levels, peaking at week 7 (mean change: 2.6 ± 0.7 mM, p = 0.001), followed by decrease at week 9 (mean change: −3.8 ± 2.5 mM, p = 0.03), along with further disease progression, with brain lesions being detected on T₂WI.

Conclusion

Using brain ¹H MRS, we demonstrated significant increase in intracerebral lactate levels in a mouse model of Leigh syndrome. Additionally, we demonstrated that intracerebral lactate is a useful biomarker of mitochondrial disease progression at stages preceding the development of brain lesions.

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How far can regulating TRIM16 help reduce malignant transformation of OPMD’s to OSCC?

Publication date: Available online 18 January 2019

Source: Oral Oncology

Author(s): Samapika Routray

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Beta human papillomaviruses in middle ear squamous cell carcinoma

Publication date: Available online 18 January 2019

Source: Oral Oncology

Author(s): Francesca Paolini, Claudia Bonomo, Irene Terrenato, Annarita Pennetti, Renato Covello, Giovanni Cristalli, Aldo Venuti

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Detection of increased intracerebral lactate in a mouse model of Leigh syndrome using proton MR spectroscopy

Publication date: Available online 19 January 2019

Source: Magnetic Resonance Imaging

Author(s): Yusuke Takahashi, Hidetaka Kioka, Yasunori Shintani, Akiko Ohki, Seiji Takashima, Yasushi Sakata, Takahiro Higuchi, Shigeyoshi Saito

Abstract

Purpose

To establish a brain proton magnetic resonance spectroscopy (¹H MRS) experimental system using a mouse model of Leigh syndrome for monitoring intracerebral lactate levels as a biomarker of mitochondrial disease progression.

Materials and methods

Brain ¹H MRS was performed in the Ndufs4 homozygous knockout (KO) mice, a mouse model of Leigh syndrome, and control mice on a horizontal 7.0-T magnetic resonance imaging system at age 5–9 weeks. In a subset of KO mice, survival analysis was performed according to the median of the intracerebral lactate levels. In addition, in KO mice alive until 9 weeks of age, both ¹H MRS and T₂-weighted imaging (T₂WI) were longitudinally performed in the same individuals at 5, 7, and 9 weeks of age.

Results

Brain ¹H MRS demonstrated increased lactate levels in KO mice compared with control mice (6.4 ± 1.2 mM vs. 3.3 ± 0.8 mM, p < 0.0001). The increased intracerebral lactate levels were already observed at 5 weeks of age, while no obvious abnormal findings were detected in T₂WI. Notably, an increased lactate level of >5.94 mM at week 5 was associated with a poor prognosis (median survival days: 24.5 vs. 42 days, log-rank p = 0.03). Longitudinal ¹H MRS experiments revealed temporal increase of intracerebral lactate levels, peaking at week 7 (mean change: 2.6 ± 0.7 mM, p = 0.001), followed by decrease at week 9 (mean change: −3.8 ± 2.5 mM, p = 0.03), along with further disease progression, with brain lesions being detected on T₂WI.

Conclusion

Using brain ¹H MRS, we demonstrated significant increase in intracerebral lactate levels in a mouse model of Leigh syndrome. Additionally, we demonstrated that intracerebral lactate is a useful biomarker of mitochondrial disease progression at stages preceding the development of brain lesions.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2TXc7ya

How far can regulating TRIM16 help reduce malignant transformation of OPMD’s to OSCC?

Publication date: Available online 18 January 2019

Source: Oral Oncology

Author(s): Samapika Routray

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2R13r84

Beta human papillomaviruses in middle ear squamous cell carcinoma

Publication date: Available online 18 January 2019

Source: Oral Oncology

Author(s): Francesca Paolini, Claudia Bonomo, Irene Terrenato, Annarita Pennetti, Renato Covello, Giovanni Cristalli, Aldo Venuti

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National Impact of 13-Valent Pneumococcal Conjugate Vaccine on Ambulatory Care Visits for Otitis Media in Children under 5 Years in the United States

Publication date: Available online 19 January 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Xiaofeng Zhou, Cynthia de Luise, Michael Gaffney, Catharine W. Burt, Daniel A. Scott, Nicolle Gatto, Kimberly J. Center

Abstract

Objective

The 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) were approved in the US in 2000 and 2010, respectively, for active immunization against invasive disease caused by all vaccine serotypes and otitis media (OM) caused by 7 serotypes common to both vaccines, starting at ∼6 weeks of age. This study assessed the impact of PCV13 on OM by evaluating changes in US ambulatory care visit rates between the period before PCV7 (1997-1999), during PCV7 (2001–2009), and after the introduction of PCV13 (2011-2013) among US children <5 years old.

Methods

This ecological study used US National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data. Trend analyses using weighted least-squares regression and mean visit rates were calculated for OM and two control endpoints not likely to be related to either vaccine (skin rash and trauma).

Results

Among children <5 and <2 years old, the observed reduction in OM visit rates was 22% (95%CI: 12%-32%) and 24% (95%CI: 13%-35%) when comparing PCV13 to PCV7 periods, and 41% (95%CI: 30%-52%) and 48% (95%CI: 37%-59%) when comparing PCV13 to pre-PCV7 periods. Visit rates for skin rash and trauma remained stable.

Conclusion

Significant reductions in US ambulatory care visit rates for OM were observed among children aged <5 years after introduction of PCV13 compared to the periods before and during PCV7; reductions were greatest among children <2 years old. The reductions beyond the PCV7 period support the effectiveness of the vaccine's 6 additional serotypes in preventing OM.

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Effectiveness and Safety of Chinese Herbal Medicine for Pediatric Adenoid Hypertrophy: a meta-analysis

Publication date: Available online 19 January 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Ya-Lei Sun, Hai-Tao Zheng, Jia-Lei Tao, Ming-Chen Jiang, Chan-Chan Hu, Xin-Min Li, Bin Yuan

Abstract

Objective

Chinese herbal medicine has been gradually used to treat pediatric adenoid hypertrophy. This meta-analysis were conducted to evaluate the clinical efficacy and safety of Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy.

Methods

Randomized controlled trials involving Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy were identified from Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang Database and VIP Information Database. The methodological quality of trials was evaluated with Cochrane Handbook criteria, and the Cochrane Collaboration's Review Manager 5.3 software was used for Meta-analysis.

Results

A total of 13 valid articles involving 1038 patients were included.The meta-analysis showed that: Compared with western medicine treatment, Chinese herbal medicine significantly improved clinical efficacy (RR=1.33, 95% CI [1.24,1.43]), and significantly decreased A/N ratio (MD=-0.04,95%CI[-0.05,-0.03]). Chinese herbal medicine also prominently improved the quality of life (MD=-4.77,95%CI[-8.35,-1.20]). Meanwhile, it dramatically improved snoring (MD=-0.46,95%CI[-0.62,-0.30]); mouth breathing (MD=-0.52,95%CI[-0.66,-0.39]); nasal obstruction (MD= -0.56,95%CI[-0.68,-0.45]).

Conclusion

Chinese herbal medicine has good clinical efficacy and safety on pediatric adenoid hypertrophy, which need to be confirmed by high quality, multiple-center, large sample randomized controlled trials.

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National Impact of 13-Valent Pneumococcal Conjugate Vaccine on Ambulatory Care Visits for Otitis Media in Children under 5 Years in the United States

Publication date: Available online 19 January 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Xiaofeng Zhou, Cynthia de Luise, Michael Gaffney, Catharine W. Burt, Daniel A. Scott, Nicolle Gatto, Kimberly J. Center

Abstract

Objective

The 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) were approved in the US in 2000 and 2010, respectively, for active immunization against invasive disease caused by all vaccine serotypes and otitis media (OM) caused by 7 serotypes common to both vaccines, starting at ∼6 weeks of age. This study assessed the impact of PCV13 on OM by evaluating changes in US ambulatory care visit rates between the period before PCV7 (1997-1999), during PCV7 (2001–2009), and after the introduction of PCV13 (2011-2013) among US children <5 years old.

Methods

This ecological study used US National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data. Trend analyses using weighted least-squares regression and mean visit rates were calculated for OM and two control endpoints not likely to be related to either vaccine (skin rash and trauma).

Results

Among children <5 and <2 years old, the observed reduction in OM visit rates was 22% (95%CI: 12%-32%) and 24% (95%CI: 13%-35%) when comparing PCV13 to PCV7 periods, and 41% (95%CI: 30%-52%) and 48% (95%CI: 37%-59%) when comparing PCV13 to pre-PCV7 periods. Visit rates for skin rash and trauma remained stable.

Conclusion

Significant reductions in US ambulatory care visit rates for OM were observed among children aged <5 years after introduction of PCV13 compared to the periods before and during PCV7; reductions were greatest among children <2 years old. The reductions beyond the PCV7 period support the effectiveness of the vaccine's 6 additional serotypes in preventing OM.

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

Effectiveness and Safety of Chinese Herbal Medicine for Pediatric Adenoid Hypertrophy: a meta-analysis

Publication date: Available online 19 January 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Ya-Lei Sun, Hai-Tao Zheng, Jia-Lei Tao, Ming-Chen Jiang, Chan-Chan Hu, Xin-Min Li, Bin Yuan

Abstract

Objective

Chinese herbal medicine has been gradually used to treat pediatric adenoid hypertrophy. This meta-analysis were conducted to evaluate the clinical efficacy and safety of Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy.

Methods

Randomized controlled trials involving Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy were identified from Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang Database and VIP Information Database. The methodological quality of trials was evaluated with Cochrane Handbook criteria, and the Cochrane Collaboration's Review Manager 5.3 software was used for Meta-analysis.

Results

A total of 13 valid articles involving 1038 patients were included.The meta-analysis showed that: Compared with western medicine treatment, Chinese herbal medicine significantly improved clinical efficacy (RR=1.33, 95% CI [1.24,1.43]), and significantly decreased A/N ratio (MD=-0.04,95%CI[-0.05,-0.03]). Chinese herbal medicine also prominently improved the quality of life (MD=-4.77,95%CI[-8.35,-1.20]). Meanwhile, it dramatically improved snoring (MD=-0.46,95%CI[-0.62,-0.30]); mouth breathing (MD=-0.52,95%CI[-0.66,-0.39]); nasal obstruction (MD= -0.56,95%CI[-0.68,-0.45]).

Conclusion

Chinese herbal medicine has good clinical efficacy and safety on pediatric adenoid hypertrophy, which need to be confirmed by high quality, multiple-center, large sample randomized controlled trials.

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Novel Proteasome Assembly Chaperone mutations in PSMG2/PAC2, cause the autoinflammatory interferonopathy, CANDLE/PRAAS4

Publication date: Available online 18 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Adriana A. de Jesus, Anja Brehm, Rachel VanTries, Pascal Pillet, Anne-Sophie Parentelli, Gina A. Montealegre Sanchez, Zuoming Deng, Isabelle Koné Paut, Raphaela Goldbach-Mansky, Elke Krüger

Summary

Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) is a rare autoinflammatory interferonopathy caused by additive loss-of-function mutations in proteasome genes. Mutations in the proteasome chaperone, PSMG2/PAC2 are a novel cause of CANDLE.

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Regulatory cells in the skin: pathophysiological role and potential targets for anti-inflammatory therapies

Publication date: Available online 18 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Sagar Uttarkar, Nicolo Costantino Brembilla, Wolf-Henning Boehncke

Abstract

Inflammation is a fundamental defence mechanism to protect the body from danger, which becomes potentially harmful if it turns chronic. Therapeutic strategies aimed at specifically blocking pro-inflammatory signals - particularly cytokines such as interleukin-4, interleukin-6, interleukin-13, interleukin-17A or tumour necrosis factor α - have substantially improved our ability to effectively and safely treat chronic inflammatory diseases. Much less efforts have been made to better understand the role of potential anti-inflammatory mechanisms. Here, we summarize the current understanding of regulatory cell populations in the context of chronic inflammation, namely macrophages, Langerhans cells, myeloid-derived suppressor cells, regulatory T and B lymphocytes. Emphasis is given to the skin as many different immune related diseases occur in the skin. Development, phenotype, function, and evidence for their role in animal models of inflammation as well as in the corresponding human diseases are described. Finally, the feasibility of using regulatory cells as targets for potentially disease-modifying therapeutic strategies is discussed.

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Systemic Antibody Responses to Gut Commensal Bacteria: How and Why Do I Know You?

Publication date: Available online 18 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Peter J. Mannon

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History and evolution of the Journal of Neuroradiology

Publication date: February 2019

Source: Journal of Neuroradiology, Volume 46, Issue 1

Author(s): Douraied Ben Salem

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Tribute to Anne Bertrand (1978–2018): Neuroradiologist, scientist, teacher and friend

Publication date: Available online 18 January 2019

Source: Journal of Neuroradiology

Author(s): Didier Dormont, Noam Ben-Eliezer, Ninon Burgos, Olivier Colliot, Fabrizio De Vico Fallani, Marc Dhenain, Stanley Durrleman, Stéphane Epelbaum, Marie-Odile Habert, Isabelle Le Ber, Jean-François Meder, Yves Menu, Catherine Oppenheim, Youssef Z. Wadghiri

Abstract

Anne Bertrand passed away on March 2nd 2018. She was in a touring-skiers group led by a guide and swept by an avalanche in the French Alps. This paper is a tribute to Anne and an attempt, by some of her closest colleagues, to provide an overview of her major contributions.

Anne Bertrand was a rising star of the neuroimaging community who traced innovative paths at the interface of basic science and clinical neuroradiology. From the very beginning of her career, she had been interested in the cross-fertilization between research and medical practice. After an MD and a specialization in neuroradiology, she prepared a PhD in preclinical imaging at the French Atomic Energy Commission (CEA) and at New York University. She was then appointed as Senior Neuroradiologist (at the Pitié-Salpêtrière and then Saint-Antoine Hospital in Paris) and Associate Professor (Sorbonne University). Simultaneously, she continued to develop her research activities in the ARAMIS Laboratory at the Brain and Spinal Cord Institute (ICM).

Her main field of interest was neuroimaging of dementias. In a short time, she made important and exceptionally diverse contributions to the understanding, detection, diagnosis and tracking of these disorders (including Alzheimer's disease and fronto-temporal lobar degeneration) using advanced multimodal neuroimaging techniques. They will be a source of inspiration for all of us. Anne was not only an outstandingly bright scientist but also enlightening by her personal qualities: joy, openness, kindness and generosity.

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Novel Proteasome Assembly Chaperone mutations in PSMG2/PAC2, cause the autoinflammatory interferonopathy, CANDLE/PRAAS4

Publication date: Available online 18 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Adriana A. de Jesus, Anja Brehm, Rachel VanTries, Pascal Pillet, Anne-Sophie Parentelli, Gina A. Montealegre Sanchez, Zuoming Deng, Isabelle Koné Paut, Raphaela Goldbach-Mansky, Elke Krüger

Summary

Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) is a rare autoinflammatory interferonopathy caused by additive loss-of-function mutations in proteasome genes. Mutations in the proteasome chaperone, PSMG2/PAC2 are a novel cause of CANDLE.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2DmOxp5

Regulatory cells in the skin: pathophysiological role and potential targets for anti-inflammatory therapies

Publication date: Available online 18 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Sagar Uttarkar, Nicolo Costantino Brembilla, Wolf-Henning Boehncke

Abstract

Inflammation is a fundamental defence mechanism to protect the body from danger, which becomes potentially harmful if it turns chronic. Therapeutic strategies aimed at specifically blocking pro-inflammatory signals - particularly cytokines such as interleukin-4, interleukin-6, interleukin-13, interleukin-17A or tumour necrosis factor α - have substantially improved our ability to effectively and safely treat chronic inflammatory diseases. Much less efforts have been made to better understand the role of potential anti-inflammatory mechanisms. Here, we summarize the current understanding of regulatory cell populations in the context of chronic inflammation, namely macrophages, Langerhans cells, myeloid-derived suppressor cells, regulatory T and B lymphocytes. Emphasis is given to the skin as many different immune related diseases occur in the skin. Development, phenotype, function, and evidence for their role in animal models of inflammation as well as in the corresponding human diseases are described. Finally, the feasibility of using regulatory cells as targets for potentially disease-modifying therapeutic strategies is discussed.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2U1BTBm

Systemic Antibody Responses to Gut Commensal Bacteria: How and Why Do I Know You?

Publication date: Available online 18 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Peter J. Mannon

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

History and evolution of the Journal of Neuroradiology

Publication date: February 2019

Source: Journal of Neuroradiology, Volume 46, Issue 1

Author(s): Douraied Ben Salem

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Editorial Board

Publication date: February 2019

Source: Journal of Neuroradiology, Volume 46, Issue 1

Author(s):

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