Good (and Bad) Ways to Help a Dog Afraid of Fireworks

You are more important than you think 

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ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma

Publication date: Available online 29 June 2017
Source:Cancer Cell
Author(s): Matteo Marchesini, Yamini Ogoti, Elena Fiorini, Anil Aktas Samur, Luigi Nezi, Marianna D'Anca, Paola Storti, Mehmet Kemal Samur, Irene Ganan-Gomez, Maria Teresa Fulciniti, Nipun Mistry, Shan Jiang, Naran Bao, Valentina Marchica, Antonino Neri, Carlos Bueso-Ramos, Chang-Jiun Wu, Li Zhang, Han Liang, Xinxin Peng, Nicola Giuliani, Giulio Draetta, Karen Clise-Dwyer, Hagop Kantarjian, Nikhil Munshi, Robert Orlowski, Guillermo Garcia-Manero, Ronald A. DePinho, Simona Colla
Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage. The intimate link between 1q21-amplified ILF2 and the regulation of RNA splicing of DNA repair genes may be exploited to optimize the use of DNA-damaging agents in patients with high-risk MM.

Graphical abstract

Teaser

Marchesini et al. show that in multiple myeloma the overexpression of ILF2, resulting from chromosome 1q21 amplification, drives resistance to DNA-damaging agents partly by modulating the interaction between YB-1 and the splicing factor U2AF65 to promote the processing and stabilization of transcripts involved in homologous recombination.


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Endogenous endophthalmitis and osteomyelitis associated with interleukin 17 inhibitor treatment for psoriasis in a patient with diabetes

A 64-year-old man with type 2 diabetes mellitus and plaque psoriasis presented to the emergency room with 3 days of progressive right eye pain and decreased vision. After extensive workup and multidisciplinary team effort, the patient was diagnosed with and treated for unilateral endogenous methicillin-sensitive Staphylococcus aureus endophthalmitis, bacteraemia and osteomyelitis of the foot. The patient had been started on the interleukin 17 (IL-17) inhibitor secukinumab for his treatment-resistant plaque psoriasis 4 weeks prior to presentation. After treatment, his final vision was light perception and the foot infection resolved without sequelae. To our knowledge, this is the first reported case of both endogenous endophthalmitis and osteomyelitis associated with an IL-17 inhibitor.

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Intrinsic and Extrinsic Causes of Malignancies in Primary Immunodeficiency Disorders

Malignancies occur with a higher incidence rate and manifest earlier in life in patients with primary immunodeficiency disorders (PID) than in the general population. However, no universal mechanism of malignancy predisposition in PID can been determined. Despite the strong support for the physiological role of tumor immunosurveillance and increasing success of strategies in immunological tumor therapy, which include checkpoint inhibition, monoclonal antibodies, and engineered T cell antigen receptors, the incidence and pattern of malignancies in PID do not reflect an increased tumor immune escape per se.

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An elusive ciliopathy: Joubert syndrome

The police brought a 65-year-old female patient to the EADU after being found 'roaming the streets' in an apparent state of confusion. This was her third admission under the same circumstances during the last 3 years. Neurological examination revealed (1) cognitive impairment, (2) oculomotor apraxia, (3) abnormal cancellation of vestibular ocular reflex, (4) mild ataxia and (5) mild hypotonia. Renal function was abnormal and liver function was normal. No retinal disturbance was found. The head CT on admission was normal for stroke and the lumbar puncture was negative for encephalitis. Her brain MRI showed 'molar tooth sign', suggestive of Joubert syndrome, which was confirmed by genetic testing showing anomalous NPHP1 gene

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Depression links to physical health decline in cancer caregivers

People who care for a family member with cancer show a steady decline in their own physical health, a study in the journal Cancer has found.1The researchers found that symptoms of depression were the...

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Items dispensed in England rise sharply in 10 years

The number of drugs dispensed in the community has risen sharply in the past 10 years, annual figures of prescribing rates have shown.1Data from NHS Digital show that 1.1 billion items were dispensed...

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Subclinical Hypothyroidism

Subclinical Hypothyroidism:

New England Journal of Medicine, Volume 376, Issue 26, Page 2556-2565, June 2017.

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Acute Neuroinflammation Promotes Cell Responses to 1800 MHz GSM Electromagnetic Fields in the rat Cerebral Cortex

Erratum to: Acute Neuroinflammation Promotes Cell Responses to 1800 MHz GSM Electromagnetic Fields in the rat Cerebral Cortex:







Neurotox Res. 2017 Jun 3. doi: 10.1007/s12640-017-9756-3. [Epub ahead of print]

Acute Neuroinflammation Promotes Cell Responses to 1800 MHz GSM Electromagnetic Fields in the Rat Cerebral Cortex.



Lameth J1, Gervais A1, Colin C1, Lévêque P2, Jay TM3, Edeline JM4, Mallat M5.

Author information

1

Sorbonne Universités, UPMC Univ Paris 06, INSERM U.1127, CNRS, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-Salpêtrière, Bat. ICM, 47 boulevard de l'Hôpital, F-75013, Paris, France.

2

Université de Limoges, CNRS, XLIM, UMR 7252, 123 avenue Albert Thomas, F-87000, Limoges, France.

3

Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, UMR_S894 INSERM, Université Paris Descartes, 102-108 rue de la Santé, 75014, Paris, France.

4

Paris Saclay Institute of Neuroscience, Neuro-PSI, UMR 9197 CNRS, Université Paris-Sud, 91405, Orsay cedex, France.

5

Sorbonne Universités, UPMC Univ Paris 06, INSERM U.1127, CNRS, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-Salpêtrière, Bat. ICM, 47 boulevard de l'Hôpital, F-75013, Paris, France. michel.mallat@upmc.fr.

Abstract

Mobile phone communications are conveyed by radiofrequency (RF) electromagnetic fields, including pulse-modulated global system for mobile communications (GSM)-1800 MHz, whose effects on the CNS affected by pathological states remain to be specified. Here, we investigated whether a 2-h head-only exposure to GSM-1800 MHz could impact on a neuroinflammatory reaction triggered by lipopolysaccharide (LPS) in 2-week-old or adult rats. We focused on the cerebral cortex in which the specific absorption rate (SAR) of RF averaged 2.9 W/kg. In developing rats, 24 h after GSM exposure, the levels of cortical interleukin-1ß (IL1ß) or NOX2 NADPH oxidase transcripts were reduced by 50 to 60%, in comparison with sham-exposed animals (SAR = 0), as assessed by RT-qPCR. Adult rats exposed to GSM also showed a 50% reduction in the level of IL1ß mRNA, but they differed from developing rats by the lack of NOX2 gene suppression and by displaying a significant growth response of microglial cell processes imaged in anti-Iba1-stained cortical sections. As neuroinflammation is often associated with changes in excitatory neurotransmission, we evaluated changes in expression and phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult cerebral cortex by Western blot analyses. We found that GSM exposure decreased phosphorylation at two residues on the GluA1 AMPAR subunit (serine 831 and 845). The GSM-induced changes in gene expressions, microglia, and GluA1 phosphorylation did not persist 72 h after RF exposure and were not observed in the absence of LPS pretreatment. Together, our data provide evidence that GSM-1800 MHz can modulate CNS cell responses triggered by an acute neuroinflammatory state.

KEYWORDS:

AMPA receptor; Electromagnetic fields; Lipopolysaccharide; Microglia; Mobile phone; Neuroinflammation; Radiofrequency

PMID: 28578480 DOI: 10.1007/s12640-017-9756-3

• Authors
• Authors and affiliations

• Julie Lameth
• Annie Gervais
• Catherine Colin
• Philippe Lévêque
• Thérèse M. Jay
• Jean-Marc Edeline
• Michel MallatEmail author

• Julie Lameth
  • 1
• Annie Gervais
  • 1
• Catherine Colin
  • 1
• Philippe Lévêque
  • 2
• Thérèse M. Jay
  • 3
• Jean-Marc Edeline
  • 4
• Michel Mallat
  • 1
  Email author

1. 1.Sorbonne Universités, UPMC Univ Paris 06, INSERM U.1127, CNRS, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-SalpêtrièreParisFrance
2. 2.Université de Limoges, CNRS, XLIM, UMR 7252LimogesFrance
3. 3.Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, UMR_S894 INSERM, Université Paris DescartesParisFrance
4. 4.Paris Saclay Institute of Neuroscience, Neuro-PSI, UMR 9197 CNRS, Université Paris-SudOrsay cedexFrance

ORIGINAL ARTICLE

First Online:03 June 2017

Received:13 February 2017Revised:16 May 2017Accepted:19 May 2017

DOI: 10.1007/s12640-017-9756-3

Cite this article as:Lameth, J., Gervais, A., Colin, C. et al. Neurotox Res (2017). doi:10.1007/s12640-017-9756-3

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Abstract

Mobile phone communications are conveyed by radiofrequency (RF) electromagnetic fields, including pulse-modulated global system for mobile communications (GSM)-1800 MHz, whose effects on the CNS affected by pathological states remain to be specified. Here, we investigated whether a 2-h head-only exposure to GSM-1800 MHz could impact on a neuroinflammatory reaction triggered by lipopolysaccharide (LPS) in 2-week-old or adult rats. We focused on the cerebral cortex in which the specific absorption rate (SAR) of RF averaged 2.9 W/kg. In developing rats, 24 h after GSM exposure, the levels of cortical interleukin-1ß (IL1ß) or NOX2 NADPH oxidase transcripts were reduced by 50 to 60%, in comparison with sham-exposed animals (SAR = 0), as assessed by RT-qPCR. Adult rats exposed to GSM also showed a 50% reduction in the level of IL1ß mRNA, but they differed from developing rats by the lack of NOX2 gene suppression and by displaying a significant growth response of microglial cell processes imaged in anti-Iba1-stained cortical sections. As neuroinflammation is often associated with changes in excitatory neurotransmission, we evaluated changes in expression and phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult cerebral cortex by Western blot analyses. We found that GSM exposure decreased phosphorylation at two residues on the GluA1 AMPAR subunit (serine 831 and 845). The GSM-induced changes in gene expressions, microglia, and GluA1 phosphorylation did not persist 72 h after RF exposure and were not observed in the absence of LPS pretreatment. Together, our data provide evidence that GSM-1800 MHz can modulate CNS cell responses triggered by an acute neuroinflammatory state.

Keywords

Electromagnetic fields Radiofrequency Mobile phone Neuroinflammation Microglia AMPA receptor Lipopolysaccharide 

An erratum to this article is available at http://ift.tt/2tse6Av.

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Funding information

Funder Name	Grant Number	Funding Note
French National Research Program for Environmental and Occupational health of ANSES	2013/2/03 and 2015/2RF/12
Institut National de l'environnement et des risques (INERIS)	DRC-13-135967-08716A
program"Investissements d'avenir"	ANR-10-IAIHU-06

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Increased activation of the hippocampus during a Chinese character subvocalization task in adults with cleft lip and palate palatoplasty and speech therapy.

Increased activation of the hippocampus during a Chinese character subvocalization task in adults with cleft lip and palate palatoplasty and speech therapy.: This study aimed to explore brain activation in patients with cleft lip and palate (CLP) using a Chinese character subvocalization task, in which the stimuli were selected from a clinical articulation evaluation test. CLP is a congenital disability. Individuals with CLP usually have articulation disorder caused by abnormal lip and palate structure. Previous studies showed that primary somatosensory and motor areas had a significant difference in activation in patients with CLP. However, whether brain activation was restored to a normal level after palatoplasty and speech rehabilitation is not clear. Two groups, adults after palatoplasty with speech training and age-matched and sex-matched controls, participated in this study. Brain activation during Chinese character subvocalization task and behavioral data were recorded using functional MRI. Patients with CLP responded to the target significantly more slowly compared with the controls, whereas no significant difference in accuracy was found between the groups. Brain activation had similar patterns between groups. Broca's area, Wernicke's area, motor areas, somatosensory areas, and insula in both hemispheres, and the dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex in the right hemisphere were activated in both groups, with no statistically significant difference. Furthermore, the two-sample t-test showed that the hippocampus in the left hemisphere was activated significantly in patients with CLP compared with the controls. The results suggested that the hippocampus might be involved in the language-related neural circuit in patients with CLP and play a role of pronunciation retrieval to help patients with CLP to complete the pronunciation effectively.

(C) 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Effects of Src kinase inhibition on expression of pro-caspase-2 after brain hypoxia

 in a piglet animal model.: Caspase-2 has features of both initiator and effector caspases. Previously, we have shown that brain hypoxia-induced production of caspases 1, 3, 8, and 9 is Src kinase mediated, a nonreceptor intracellular family of kinases. The present study tests the hypothesis that hypoxia results in increased expression of caspase-2 and this effect is mediated by Src kinase. Two to three days old newborn piglets were subjected to normoxia, hypoxia (Hx, FiO2 7%), and Src kinase inhibition (using PP2, 1 mg/kg, intravenous), followed by 30 min of acute hypoxia (Hx+PP2). ATP and phosphocreatine were determined biochemically to verify energy molecule depletion in the hypoxic groups. The cytosolic brain function was isolated and a western blot analysis was carried out using an antibody specific for the caspase-2. The immune-complex band density was expressed as OD/mm2. Caspase-2 expression was increased two-fold in the Hx group. After Src kinase inhibition followed by hypoxia, caspase-2 expression was similar to normoxia levels. We conclude that hypoxia results in increased expression of caspase-2 protein in the cytosolic fraction of the cerebral cortex of the newborn piglets. This increase is mediated by Src kinase.

(C) 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

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A magnetoencephalography investigation of coherence source imaging in panic disorder.

A magnetoencephalography investigation of coherence source imaging in panic disorder.: Limbic and frontal structures are largely implicated in panic disorder (PD). Decreased coherence imaging values, as determined by magnetoencephalography (MEG), are suggestive of decreased or inefficient communication among these structures. We have previously demonstrated that coherence source imaging (CSI) values could be similar or higher in some PD patients. The purpose of the current investigation was to replicate these finding in a larger sample. Nine strictly diagnosed PD patients and nine age-matched and sex-matched healthy controls were examined. The CSI-MEG values of 26 frontotemporal regions (FTRs) and 28 extra-frontotemporal regions (ex-FTR; Brodmann areas) were determined for each participant. MEG scans were acquired using a 151-channel whole-head biomagnetometer system. Despite the relatively small sample size, CSI values were significantly lower in a number of FTRs in PD patients. In none of the ex-FTRs (i.e. posterior regions) were there differences between panic and control groups. The above data add to the complexity of understanding the nature of the pathophysiology of PD. Our finding of decreased focal coherence imaging values may reflect decreased excitability in these areas. The preliminary finding could be interpreted as an inhibitory process guarding against the spread of activity in closer hyperexcitable areas as seen in epilepsy. The current data provide evidence for dysfunctional communication within the frontotemporal structures. The findings have implications for the understanding of the neural circuitry underlying PD.

(C) 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

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The relationship between cognitive style and event-related potentials during auditory and somatosensory Go/No-go paradigms.

The relationship between cognitive style and event-related potentials during auditory and somatosensory Go/No-go paradigms.: Cognitive style including field dependence/independence (FDI) is an important factor affecting individual personalities. The present study aimed to clarify the relationship between cognitive styles and the characteristics of cognitive processing using event-related potentials. We used the Embedded-Figures Test to assess the cognitive styles [field dependence (FD), field independence (FI)] of the individuals, and individuals performed auditory and somatosensory Go/No-go paradigms. Participants were divided into two groups (FD and FI) on the basis of EFT scores. Reaction times during auditory Go/No-go paradigms were significantly earlier in the FI group than in the FD group, and response variabilities and omission errors were significantly smaller in the FI group than in the FD group. Go-P300 and No-go-P300 amplitudes were significantly larger in the FI group than in the FD group, suggesting that the FI group exhibited greater neural activity for response executive and inhibitory processing. No significant differences were observed in the amplitudes or latencies of auditory N100 and somatosensory N140 components between the FI and FD groups, suggesting that auditory-related and somatosensory-related neural activities were not related to FDI cognitive styles. Our results showed that FDI cognitive styles were related to neural activity for response executive and inhibitory processing.

(C) 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Dysphagia in Motor Neuron Diseases (MND)

Trends in Research Literature Describing Dysphagia in Motor Neuron Diseases (MND): A Scoping Review:

Abstract

Dysphagia in motor neuron diseases (MNDs) is highly complex, affecting all stages of swallowing and leading to impaired swallowing safety and efficiency. In order to explore the degree to which research is capturing the symptom of dysphagia in MND, we conducted a scoping review of the existing literature. The primary aims of this review were to identify common themes within the literature on dysphagia in MND, explore patterns and trends in research focus, and identify if any imbalances exist between the research themes related to dysphagia description and management. A comprehensive search strategy yielded 1690 unique articles for review. Following relevance screening, a total of 157 articles were included in the synthesis. Relevant data and keywords were extracted from each article and grouped into themes. Frequency estimates were calculated for each theme to identify trends across research literature. Swallowing impairment in MNDs is described in a variety of ways across current research. The most commonly reported theme was Aspiration/Penetration, mentioned in 73.2% of all included articles; a significant imbalance was identified between reports of swallowing safety and efficiency (p = 0.008). The most frequently reported theme related to dysphagia management was Enteral Nutrition, and very few studies have reported on the efficacy of Rehabilitation/Compensatory recommendations. It is suggested that researchers and clinicians remain mindful of imbalances and gaps in research, and aim to characterize dysphagia in MNDs in a comprehensive manner. Further research investigating discrete, measureable changes in swallowing pathophysiology would be beneficial to delineate the key factors contributing to impaired swallowing safety and efficiency.

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The clinical impact of 18 F–FDG PET/CT in extracranial pediatric germ cell tumors

The clinical impact of 18 F–FDG PET/CT in extracranial pediatric germ cell tumors:

Abstract

Background

Extracranial germ cell tumors are an uncommon pediatric malignancy with limited information on the clinical impact of ¹⁸F–fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the literature.

Objective

The purpose of this study was to evaluate and compare the clinical impact on management of ¹⁸F–FDG PET/CT with diagnostic computed tomography (CT) in pediatric extracranial germ cell tumor.

Materials and methods

The list of ¹⁸F–FDG PET/CT performed for extracranial germ cell tumor between May 2007 and November 2015 was obtained from the nuclear medicine database. ¹⁸F–FDG PET/CT and concurrent diagnostic CT were obtained and independently reviewed. Additionally, the patients' charts were reviewed for duration of follow-up and biopsy when available. The impact of ¹⁸F–FDG PET/CT compared with diagnostic CT on staging and patient management was demonstrated by chart review, imaging findings and follow-up studies.

Results

During the study period, 9 children (5 males and 4 females; age range: 1.6–17 years, mode age: 14 years) had 11 ¹⁸F–FDG PET/CT studies for the evaluation of germ cell tumor. Diagnostic CTs were available for comparison in 8 patients (10 ¹⁸F–FDG PET/CT studies). The average interval between diagnostic CT and PET/CT was 7.2 days (range: 0–37 days). In total, five lesions concerning for active malignancy were identified on diagnostic CT while seven were identified on PET/CT. Overall, ¹⁸F–FDG PET/CT resulted in a change in management in 3 of the 9 patients (33%).

Conclusion

¹⁸F–FDG PET/CT had a significant impact on the management of pediatric germ cell tumors in this retrospective study. Continued multicenter studies are required secondary to the rarity of this tumor to demonstrate the benefit of ¹⁸F–FDG PET/CT in particular clinical scenarios.

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Linear Unilateral Basaloid Follicular Hamartoma Following Blaschko's Lines: Two Case Reports and Review of the Literature

Linear Unilateral Basaloid Follicular Hamartoma Following Blaschko's Lines: Two Case Reports and Review of the Literature:

Abstract

Basaloid follicular hamartoma (BFH) is a rare follicular malformation characterized by variable clinical presentations and identical histopathologic features. We present the cases of a 3-month-old boy and an 8-year-old boy with linear unilateral BFH. To the best of our knowledge, only 14 cases of linear unilateral BFH have been described in the English-language literature.

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Variability of Delivery of Timolol for the Treatment of Infantile Hemangiomas

Variability of Delivery of Timolol for the Treatment of Infantile Hemangiomas:

Abstract

Background/Objectives

Topical timolol maleate solution or gel-forming solution is used alone or in conjunction with oral propranolol for the treatment of infantile hemangiomas. The consistency of the amount of timolol dispensed has never been evaluated. We evaluated the variability of drug delivery between different brands and formulations of timolol solution and gel-forming solution.

Methods

Five blinded volunteers sequentially dispensed five drops from each of the eight bottles containing timolol 0.5% solution or gel-forming solution. This was repeated three times per user for each bottle. The average amount of timolol dispensed was analyzed according to brand, formulation, and user for variability. The intra- and interuser variability of dispensing both formulations of timolol was also measured.

Results

Our study demonstrates statistically significant differences in the amount of timolol dispensed between timolol solution and gel-forming solution, with the latter closer to manufacturer estimates. Significant differences in the amount of timolol dispensed were noted between users regardless of the formulation or brand. Variability in the amount of timolol dispensed was greater for gel-forming solution than 0.5% solution. Inter- and intrauser variability in the amount of timolol dispensed was greater for gel-forming solution than 0.5% solution.

Conclusion

Statistically significant differences were noted in the amount of timolol dispensed according to formulation, brand, and user. Whether this is clinically significant is unknown given the lack of pharmacokinetic data available for timolol.

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