Πέμπτη 4 Ιουλίου 2019

Abnormal Child Psychology

Depression and ADHD-Related Risk for Substance Use in Adolescence and Early Adulthood: Concurrent and Prospective Associations in the MTA

Abstract

Childhood attention-deficit/hyperactivity disorder (ADHD) is prospectively linked to substance use and disorder. Depression emerging in adolescence is an understudied risk factor that may explain some of this risk. In the present study, we considered mediating and moderating roles of adolescent depression in explaining this association by using longitudinal data from the prospective 16-year follow-up of the Multimodal Treatment Study of ADHD (MTA). Participants were 547 children diagnosed with DSM-IV ADHD Combined Type, and 258 age- and sex-matched comparison children. In adolescence, depressive symptoms did not exacerbate effects of childhood ADHD on any substance use. For both groups, time-varying and average depressive symptoms were associated with more frequent use of all substances. Prospectively, we found no evidence of depression mediation to adult substance use. However, adolescent depression moderated the association between childhood ADHD and adult marijuana use. Although adults without ADHD histories used marijuana more frequently if they had elevated depressive symptoms in adolescence, marijuana use by adults with ADHD histories was independent of their adolescent depression. In adulthood, depression diagnoses and ADHD persistence continued to operate as independent, additive correlates of substance use risk. Our findings suggest a circumscribed role for depression in substance use risk that adds to, but does not alter or explain, ADHD-related risk.



Frontal Brain Asymmetry and the Trajectory of Shyness Across the Early School Years

Abstract

Although resting right frontal electroencephalogram (EEG) asymmetry has been linked to avoidance and withdrawal-related behaviors such as shyness in previous cross-sectional studies, relatively little research has examined the influence of frontal brain electrical activity on the development of shyness in children using a prospective, longitudinal study design. Here, we tested whether resting frontal EEG asymmetry predicted the trajectory of children's shyness across five assessments. Children were enrolled in the study during the summer prior to grade 1 (N = 37; Mage = 6.39 years, S.D. = 0.15 years), at which time resting frontal EEG activity and maternal report of children's shyness were collected. Mothers then reported on their child's shyness over another four follow-up assessments, spanning 2 years (winter of grade 1, summer prior to grade 2 entry, winter of grade 2, and summer prior to grade 3). Growth curve analysis revealed that children displaying greater relative right frontal EEG activity had lower levels of shyness relative to children exhibiting greater relative left frontal EEG activity at study enrollment (i.e., age 6), but displayed statistically significant linear increases in shyness across time, with the highest levels of shyness by the summer prior to grade 3 (i.e., age 8). There was, however, no relation between left frontal EEG asymmetry and change in shyness across time. These preliminary findings suggest that right frontal EEG asymmetry may reflect a biological diathesis for the growth of shyness during the early school years.



A Dynamic Examination of the Associations between Shyness, Psychological Difficulties, and Stressful Life Events during Early Adolescence

Abstract

Although numerous studies have established linkages between shyness and later psychological difficulties, most extant research did not examine variation in shyness over time in relation to variation in psychological difficulties over time or possible environmental factors of influence outside of the school context. The current study used multi-level modelling to simultaneously examine time-invariant and time-variant associations between shyness, the psychological difficulties of depressive symptoms and loneliness, and stressful life events at four waves across 1 year in a community sample of 271 young adolescents (51% boys; Mage = 11.83 years at W1). Results revealed significant time-variant and time-invariant effects when loneliness was examined as a predictor of shyness. In addition, a significant interaction effect indicated that shyness decreased over time for those young adolescents who experienced few stressful life events, highlighting an understudied moderator of risk. Overall, findings have important implications for understanding the psychological concomitants of shyness as well as etiological models of shyness.



Parenting Interacts with Oxytocin Polymorphisms to Predict Adolescent Social Anxiety Symptom Development: A Novel Polygenic Approach

Abstract

Guided by a developmental psychopathology framework, research has increasingly focused on the interplay of genetics and environment as a predictor of different forms of psychopathology, including social anxiety. In these efforts, the polygenic nature of complex phenotypes such as social anxiety is increasingly recognized, but studies applying polygenic approaches are still scarce. In this study, we applied Principal Covariates Regression as a novel approach to creating polygenic components for the oxytocin system, which has recently been put forward as particularly relevant to social anxiety. Participants were 978 adolescents (49.4% girls; Mage T1 = 13.8 years). Across 3 years, questionnaires were used to assess adolescent social anxiety symptoms and multi-informant reports of parental psychological control and autonomy support. All adolescents were genotyped for 223 oxytocin single nucleotide polymorphisms (SNPs) in 14 genes. Using Principal Covariates Regression, these SNPs could be reduced to five polygenic components. Four components reflected the underlying linkage disequilibrium and ancestry structure, whereas the fifth component, which consisted of small contributions of many SNPs across multiple genes, was strongly positively associated with adolescent social anxiety symptoms, pointing to an index of genetic risk. Moreover, significant interactions were found with this polygenic component and the environmental variables of interest. Specifically, adolescents who scored high on this polygenic component and experienced less adequate parenting (i.e., high psychological control or low autonomy support) showed the highest levels of social anxiety. Implications of these findings are discussed in the context of individual-by-environment models.



Sad, Scared, or Rejected? A Short-Term Longitudinal Study of the Predictors of Social Avoidance in Chinese Children

Abstract

The goal of the present study was to empirically examine different conceptual mechanisms previously postulated to underlie the development of social avoidance in childhood. Participants were N = 601 children (321 boys, 280 girls) attending elementary schools (Mage = 10.21 years) and middle schools (Mage = 12.77 years) in Shanghai, P.R. China. Measures of motivations for social withdrawal (shyness, unsociability, social avoidance) and socio-emotional adjustment were collected using self-reports and peer nominations at two time-points separated by 9 months. Results from cross-lagged panel analyses indicated that: (1) social avoidance and symptoms of social anxiety were not reciprocally related over time; (2) Time 1 social avoidance predicted incremental change in Time 2 peer problems (whereas Time 1 peer problems did not predict incremental change in Time 2 social avoidance); and (3) Time 1 symptoms of depression significantly predicted incremental change in Time 2 social avoidance (whereas Time 1 social avoidance did not predict incremental change in Time 2 symptoms of depression). These results provide evidence in support of depressive symptoms (but not symptoms of social anxiety or peer problems) as a salient predictor of social avoidance. Results are discussed in terms of the development and implications of social avoidance in Chinese culture.



Early Childhood Predictors of Anxiety in Early Adolescence

Abstract

This longitudinal study examined a multitude of early childhood predictors of anxiety symptoms and disorders over an 8-year period. The purpose of the study was to identify early life predictors of anxiety across childhood and early adolescence in a sample of at-risk children. The sample included 202 preschool children initially identified as behaviorally inhibited or uninhibited between the ages of 3 years 2 months and 4 years 5 months. Temperament and familial environment variables were assessed using observation and parent report at baseline. Anxiety symptoms and disorders were assessed using questionnaires and diagnostic interviews at baseline (age 4), and at age 6, 9 and 12 years. In line with our hypotheses, the findings showed that preschool children were more likely to experience anxiety symptoms and disorders over time i) when the child was inhibited, ii) when there was a history of maternal anxiety disorders or iii) when mothers displayed high levels of overinvolvement. Further, the study identified a significant interaction effect between temperament and maternal overvinvolvement such that behaviorally inhibited preschoolers had higher anxiety symptoms at age 12, only in the presence of maternal overinvolvement at age 4. The increased risk of anxiety in inhibited children was mitigated when mothers demonstrated low levels of overinvolvement at age 4. This study provides evidence of both additive and interactive effects of temperament and family environment on the development of anxiety and provides important information for the identification of families who will most likely benefit from targeted early intervention.



Predicting Temperamentally Inhibited Young Children's Clinical-Level Anxiety and Internalizing Problems from Parenting and Parent Wellbeing: a Population Study

Abstract

The aim of this study was to explore how some temperamentally inhibited young children and not others in the general population develop anxiety disorders and broader clinical-level internalizing (anxious/depressive) problems, with a focus on the family. A brief screening tool for inhibition was universally distributed to parents of children in their year before starting school across eight socioeconomically diverse government areas in Melbourne, Australia (307 preschool services). Screening identified 11% of all children as inhibited. We invited all parents of inhibited children to participate in a longitudinal prevention study. Participants were 545 parents of inhibited pre-schoolers (78% uptake) of whom 498 (91%) completed assessment one year later and 469 (86%) two years later. Parents completed questionnaires to assess parenting practices, parent wellbeing, and child internalizing problems. Parents also engaged in structured diagnostic interviews to assess child anxiety disorders. During the follow up period close to half of the inhibited young children had anxiety disorders and one in seven had clinical-level internalizing problems, with girls perhaps at higher risk. The family variables significantly predicted inhibited children's anxiety disorders and broader internalizing problems. For child anxiety disorders, overinvolved/protective parenting was particularly important for girls and boys, and poorer parent wellbeing contributed. For child anxious/depressive problems, harsh discipline was a consistent predictor for girls and boys, and poorer parent wellbeing again contributed. These etiological findings support early intervention for temperamentally inhibited young children that focuses on the family environment to prevent the development of mental health problems.



Multiple Trajectories in Anxious Solitary Youths: the Middle School Transition as a Turning Point in Development

Abstract

This study aimed to identify divergent patterns of individual continuity and change in anxious solitude (AS) in the last half of elementary school (3rd – 5th grade) and the first two years of middle school (6th – 7th grade), and test predictors and outcomes of these pathways. Participants were 688 youths (girls n = 354, 51.5%; M age at outset = 8.66 years, SD = 0.50). Latent class growth analyses identified two AS trajectory classes in elementary school (moderate-decreasing, high-increasing) and three in middle school (low-stable, low-increasing, high-decreasing). The elementary school moderate-decreasing class was two-and-a-half times more likely than others to end in the middle school low-stable class. In contrast, the elementary school high-increasing class was twice as likely as others to end in the middle school low-increasing class, and four times as likely to end in the middle school high-decreasing class. Peer exclusion predicted membership in increasing AS trajectory classes in both elementary and middle school, whereas the middle school high-decreasing AS trajectory class demonstrated decreasing peer exclusion during middle school. Likewise, inability to defend oneself predicted membership in increasing AS trajectory classes in both elementary and middle school, whereas membership in the middle school high-decreasing AS trajectory class was predicted by inability to defend oneself in elementary but not middle school. High-decreasing AS youths' improved ability to defend themselves in middle school appeared to be related to a cascade of improvements in related domains. In contrast, membership in increasing AS classes in elementary and middle school predicted symptoms of social anxiety and depression.



Multidimensional Emotion Regulation Moderates the Relation Between Behavioral Inhibition at Age 2 and Social Reticence with Unfamiliar Peers at Age 4

Abstract

Behavioral inhibition (BI), a temperament trait characterized by fear and wariness in novel situations, has been identified as a risk factor for later social reticence and avoidance of peer interactions. However, the ability to regulate fearful responses to novelty may disrupt the link between BI and socially reticent behavior. The present study examined how and whether both behaviorally-manifested and physiological indices of emotion regulation moderate the relation between BI and later social reticence. Participants in this study included 88 children followed longitudinally from ages 2 to 4. At age 2, children completed the BI Paradigm in which children's responses to novel objects and adults were observed. At age 4, children's baseline respiratory sinus arrhythmia (RSA) was assessed and mothers reported on children's negative emotionality and soothability. Social reticence at age 4 was observed during a free play session with 3 unfamiliar peers. Results from saturated path models revealed a significant two-way interaction between BI and baseline RSA and a three-way interaction between BI, negative emotionality, and baseline RSA when predicting socially reticent behavior at age 4. At high levels of baseline RSA and high levels of negative emotionality, the association between BI and social reticence was negative. The relation between BI and later social reticence was only positive and significant at low levels of baseline RSA combined with high levels of negative emotionality. The results suggest that either strong physiological regulation or low negative emotionality seems sufficient to buffer inhibited young children against later social reticence.



Developmental Trajectories of Shyness-Sensitivity from Middle Childhood to Early Adolescence in China: Contributions of Peer Preference and Mutual Friendship

Abstract

This study examined trajectories of shyness-sensitivity and the contributions of peer relationships to these trajectories in Chinese children. Participants were 1061 school-age children (537 boys), initially in fifth grade (Mage = 11 years), in China. Longitudinal data on shyness-sensitivity were collected from peer assessments once a year for four years. In addition, peer nomination data on peer acceptance-rejection and mutual friendship were collected in the initial study. Four distinct shyness-sensitivity trajectories were identified: Low-Stable, Low-Increasing, Moderate-Decreasing, and High-Stable. Children with high peer acceptance scores were more likely to be in the High-Stable and Moderate-Decreasing trajectories than in the Low-Stable and Low-Increasing trajectories. The analysis of predictors of the within-trajectory growth rate indicated that children who were more liked by peers increased their shyness-sensitivity more slowly within the Low-Increasing trajectory and that children with mutual friendship involvement decreased their shyness-sensitivity more slowly within the Moderate-Decreasing trajectory. The results suggested that positive relationships might serve to attenuate developmental changes of shyness-sensitivity within these trajectories. The results were discussed in the Chinese context.



Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Clinical Infectious Diseases

 
Advance articles alert
 
30 June 2019 - 01 July 2019
 
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Penicillin as a Potential Agent for Dual Beta-lactam Therapy for Enterococcal Endocarditis 
 
B J Tritle; T T Timbrook; M A Fisher; E S Spivak
 
 
Sources of Airborne Norovirus in Hospital Outbreaks 
 
Malin Alsved; Carl-Johan Fraenkel; Mats Bohgard; Anders Widell ; Anna Söderlund-Strand ...
 
 
Asymptomatic infection and transmission of pertussis in households: a systematic review 
 
Rodger Craig, MPH; Elizabeth Kunkel, MScPH; Natasha S Crowcroft, MD(Cantab); Meagan C Fitzpatrick, PhD ; Hester de Melker, PhD ...
 
 
Assessing the Incidence of Symptomatic Respiratory Syncytial Virus (RSV) Illness within a Prospective Birth Cohort in Managua, Nicaraguaborder= 
 
John Kubale ; Guillermina Kuan; Lionel Gresh; Sergio Ojeda; Eduardo Azziz-Baumgartner ...
 
 
If Influenza Vaccines Wane Can We Delay Vaccination Without Compromising Coverage? 
 
Nicola P Klein, M.D. Ph.D; Bruce Fireman
 
 
Waning of influenza vaccine protection: Exploring the trade-offs of changes in vaccination timing among older adults 
 
J M Ferdinands; E Alyanak; C Reed; A M Fry
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Academic Radiology

Ultrasound-guided Therapeutic Injection and Cryoablation of the Medial Plantar Proper Digital Nerve (Joplin's Nerve): Sonographic Findings, Technique, and Clinical Outcomes

Publication date: Available online 3 July 2019

Source: Academic Radiology

Author(s): Christopher J. Burke, Julien Sanchez, William R. Walter, Luis Beltran, Ronald Adler

Rationale and Objectives

The medial plantar proper digital nerve, also called Joplin's nerve, arises from the medial plantar nerve, courses along the medial hallux metatarsophalangeal joint, and can be a source of neuropathic pain due to various etiologies, following acute injury including bunion surgery and repetitive microtrauma. We describe our clinical experience with diagnostic ultrasound assessment of Joplin's neuropathy and technique for ultrasound-guided therapeutic intervention including both injection and cryoablation over a 6-year period.

Materials and Methods

Retrospective review of all diagnostic studies performed for Joplin's neuropathy and therapeutic Joplin's nerve ultrasound-guided injections and cryoablations between 2012 and 2018 was performed. Indications for therapeutic injection and cryoablation, were recorded. Studies were assessed for sonographic abnormalities related to the nerve and perineural soft tissues. Post-treatment outcomes including immediate pain scores, clinical follow-up, and periprocedural complications were documented.

Results

Twenty-four ultrasound-guided procedures were performed, including 15 perineural injections and nine cryoablations. With respect to sonographic abnormalities, nerve thickening (33%) and perineural hypoechoic scar tissue (27%) were the most common findings. The mean pain severity score prior to the therapeutic injection was 6.4/10 (range 4–10) and 0.25/10 (range 0–2) following the procedure; mean follow-up was 26.2 months (range 3–63 months). All of the cryoablation patients experienced sustained pain relief with a mean length follow-up of 3.75 months (range 0.2–10 months).

Conclusion

Therapeutic injection of Joplin's nerve is a safe and easily performed procedure under ultrasound guidance, with high rates of immediate symptom improvement. For those experiencing a relapse or recurrent symptoms, cryoablation offers an effective secondary potential treatment option.



To Score or Not to Score—The USMLE Debate Continues

Publication date: Available online 2 July 2019

Source: Academic Radiology

Author(s): Priscilla J. Slanetz



Discrepancy in Practices Related to the Use of Oral Contrast in Abdominal CT Scan

Publication date: July 2019

Source: Academic Radiology, Volume 26, Issue 7

Author(s): Shahmeer Khan, Muhammad Awais, Anwar Ahmed



Counterpoint: Why Some Imposed Structure is a Necessity in Radiology Reporting

Publication date: July 2019

Source: Academic Radiology, Volume 26, Issue 7

Author(s): Adam E. Flanders



In Opposition to Standardized Templated Reporting

Publication date: July 2019

Source: Academic Radiology, Volume 26, Issue 7

Author(s): David Mark Yousem



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

Publication date: July 2019

Source: Academic Radiology, Volume 26, Issue 7

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.



Reliability of MRI-Derived Depth of Invasion of Oral Tongue Cancer

Publication date: July 2019

Source: Academic Radiology, Volume 26, Issue 7

Author(s): Ryuji Murakami, Shinya Shiraishi, Ryoji Yoshida, Junki Sakata, Keisuke Yamana, Akiyuki Hirosue, Yoshikazu Uchiyama, Hideki Nakayama, Yasuyuki Yamashita

Rationale and Objective

To evaluate the inter-rater reliability of the magnetic resonance imaging (MRI)-derived depth of invasion (DOI) and the agreement between MRI and pathological measurements of oral tongue cancer.

Materials and Methods

The institutional review board approved this retrospective study. The study population consisted of 29 patients with clinical T2N0 oral tongue cancer treated by surgery. Routine pretreatment MRI was performed on a 3T superconducting imager. Two raters with 23 and 18 years of head-and-neck MRI experience, respectively, independently chosen MRI sequences for each patient, then delineate the tumor, and then used three protocols to measure the MRI-derived DOI: the axial reconstructed thickness (method 1), the axial invasive portion (method 2), and the coronal invasive portion (method 3). Then they consensually selected the optimal among the three methods for each patient; it was designated method 4. The Bland-Altman plots, intraclass correlation coefficients (ICCs), and the paired samples test were used. According to the median follow-up of 41 months, the relationship between the MRI-derived DOI and nodal recurrence was also investigated.

Results

The inter-rater reliability of methods 2 and 4 was excellent (ICC of 0.829 and 0.807, respectively). The correlation between MRI and pathological measurements was good for method 4 (ICC of 0.611), however, all measurements recorded on MRI were 2–3 mm larger than on pathology. No patients whose MRI-derived DOI was less than 5 mm suffered nodal recurrence.

Conclusion

The MRI-derived DOI was valuable for the preoperative staging. The optimal measurement method should be selected on a case-by-case basis.



Influence of Monoenergetic Images at Different Energy Levels in Dual-Energy Spectral CT on the Accuracy of Computer-Aided Detection for Pulmonary Embolism

Publication date: July 2019

Source: Academic Radiology, Volume 26, Issue 7

Author(s): Guangming Ma, Yuequn Dou, Shan Dang, Nan Yu, Yanbing Guo, Chuangbo Yang, Shuanhong Lu, Dong Han, Chenwang Jin

Purpose

To investigate the influence of monoenergetic images of different energy levels in spectral computed tomography (CT) on the accuracy of computer aided detection (CAD) for pulmonary embolism (PE).

Materials and Methods

CT images of 20 PE patients who underwent spectral CT pulmonary angiography were retrospectively analyzed. Nine sets of monochromatic images from 40 to 80 keV at 5 keV interval were reconstructed and then independently analyzed for detecting PE using a commercially available CAD software. Two experienced radiologists reviewed all images and recorded the number of emboli manually, which was used as the reference standard. The CAD findings for the number of PE at different energies were compared with the reference standard to determine the number of true positives and false positives with CAD and to calculate the sensitivity and false positive rate at different energies.

Result

There were 120 true emboli. The total numbers of CAD-detected PE at 40–80 keV were 48, 67, 63, 87, 106, 115, 138, 157, and 226. Images at low energies had low sensitivities and low false positive rates; images at high energies had high sensitivities and high false positive rates. At 60 keV and 65 keV, CAD achieved sensitivity at 81.67% and 84.17%, respectively and false positive rate at 7.55% and 12.17%, respectively to provide the optimum combination of high sensitivity and low false positive rate.

Conclusion

Monochromatic images of different energies in dual-energy spectral CT affect the accuracy of CAD for PE. The combination of CAD with images at 60–65 keV provides the optimum combination of high sensitivity and low false positive rate in detecting PE.



The Association Between Bronchial Wall CT Attenuation and Spirometry in Patients with Bronchial Asthma

Publication date: July 2019

Source: Academic Radiology, Volume 26, Issue 7

Author(s): Shoichiro Matsushita, Tsuneo Yamashiro, Shin Matsuoka, Kunihiro Yagihashi, Yasuo Nakajima

Rationale and Objective

The purpose of this study was to evaluate the correlation between generation-based bronchial wall attenuation on thin-section computed tomography (CT) scans and airflow limitation in patients with bronchial asthma.

Materials and Methods

This study included 28 bronchial asthma patients (13 men, 15 women; age range, 23–89 years) who underwent both chest CT and spirometry. On CT, the mean values of peak wall attenuation, wall area percentage, and luminal area were measured in the segmental, subsegmental, and sub-subsegmental bronchi of the right B1 and B10 bronchi. Correlations of the CT measurements with forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), percent predicted forced expiratory flow at 25%–75% of the FVC (%pred forced expiratory flow25–75), and percent predicted peak flow rate were evaluated with Spearman's rank correlation test.

Results

The peak wall attenuation of each generation of segmental bronchi significantly correlated with the forced expiratory volume in 1 second/FVC (B1 segmental, ρ = −0.683, p < 0.0001; B1 subsegmental, ρ = −0.875, p < 0.0001; B1 sub-subsegmental, ρ = −0.926, p < 0.0001; B10 segmental, ρ = −0.811, p < 0.0001; B10 subsegmental, ρ = −0.903, p < 0.0001; B10 sub-subsegmental ρ = −0.950, p < 0.0001). Similar correlations were found between the peak wall attenuation and %pred forced expiratory flow 25–75 or percent predicted peak flow rate. Overall, the correlation coefficients were relatively high in the more peripheral bronchial generations. In all measurements, the coefficients of the peak wall attenuations were higher than those of the wall area percentage and luminal area.

Conclusion

Peak attenuation of the bronchial wall, particularly in the peripheral bronchi, measured on CT is a good biomarker for the severity of bronchial asthma.



A Comparison of Two Hyperpolarized 129Xe MRI Ventilation Quantification Pipelines: The Effect of Signal to Noise Ratio

Publication date: July 2019

Source: Academic Radiology, Volume 26, Issue 7

Author(s): Mu He, Wei Zha, Fei Tan, Leith Rankine, Sean Fain, Bastiaan Driehuys

Rationale

Hyperpolarized 129Xe MRI enables quantitative evaluation of regional ventilation. To this end, multiple classifiers have been proposed to determine ventilation defect percentage (VDP) as well as other cluster populations. However, consensus has not yet been reached regarding which of these methods to deploy for multicenter clinical trials. Here, we compare two published classification techniques–linear-binning and adaptive K-means–to establish their limits of agreement and their robustness against reduced signal-to-noise ratio (SNR).

Methods

A total of 29 subjects (age: 38.4 ± 19.0 years) were retrospectively identified for inter-method comparison. For each 129Xe ventilation image, 7 images with reduced SNR were generated with equal decrements relative to the native SNR. All 8 sets of images were then analyzed using both methods independently to classify all lung voxels into four clusters: VDP, low-, medium-, and high-ventilation-percentage (LVP, MVP and HVP). For each cluster, the percentage of the lung it comprised was compared between the two methods, as well as how these values persisted as SNR was degraded.

Results

The limits of agreement for calculating VDP were [+0.2%, +4.0%] with a +1.5% bias for binning relative to K-means. However, the inter-method agreement for the other clusters was moderate, with biases of −5.7%, 8.1%, and −4.0% for LVP, MVP, and HVP, respectively. As SNR decreased below ∼4, both methods began reporting values that deviated substantially from the native image. By requiring VDP to remain within ≤1.8% of that calculated from the native image, the minimum tolerable SNR values were 2.4 ± 1.0 for the linear-binning, and 3.5 ± 1.5 for the K-means.

Conclusions

Both methods agree well in quantifying VDP, but agreement for LVP and MVP remains variable. We suggest a required SNR threshold be two standard deviations above the minimum value of 3.5 ± 1.5 for robust determination of VDP, suggesting a minimum SNR of 6.6. However, robust quantification of the ventilated clusters required an SNR of 13.4.



Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

The Hearing Journal

Inner Ear Drug Delivery: Tomorrow's Treatment for Hearing Loss?

By Sueanne Phan, MBA

The growing need for hearing loss treatment has spurred the development of many inner ear therapies for indications from drug ototoxicity to inner ear disorders, but significant challenges need to be overcome to turn these options into reality. Read more.

 

Malaria Drug Could Moderate Genetic Hearing Loss

By Alexis Guerra

The antimalarial drug artemisinin can potentially restore inner ear sensory cell function and hearing in those with certain types of genetic hearing loss such as Usher syndrome. Read more.

 

Hearing Loss in Children with Homozygous Sickle Cell Disease

By Andrew Stuart, PhD, CCC-A, AuD(C)

The prevalence of sensorineural hearing loss among those with sickle cell disease (SCD) is higher than the general population. Dr. Stuart presents the findings of their investigation into the medical and research databases from the Children's Hospital of Philadelphia to learn more about the emergence and prevalence of hearing loss in children with homozygous SCD. Read more.

 

Audiology Without Borders: Cultural Considerations for Hearing Care in the Nepalese Himalayas

By Sandra Eisner

The Singsa Lhomis of northeastern Nepal hold unique cultural beliefs and practices that sometimes hinder them from seeking proper audiological care. Sandra Eisner braved this challenge to promote hearing health to indigenous communities where ear disease and hearing loss are prevalent. Read more.

 

Symptoms: Dizziness with Ear Pressure

By Hamid R. Djalilian, MD, and Autefeh Sajjadi, MS

A 55-year-old woman with a history of childhood ear surgery 20 years ago comes for an evaluation of ear drainage that has been going on for two to three years. What's the diagnosis?Read more.


ONLINE EXCLUSIVE: BONUS VIDEOS

WATCH accompanying patient videos online to improve your diagnosis of this month's Clinical Consultation Case. 

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Facial Plastic Surgery Clinics

Relevant Topical Skin Care Products for Prevention and Treatment of Aging Skin
Options for skin care are varied. New products are introduced constantly and it is important for the practitioner to have an understanding of products that impart beneficial results for aging skin. Educating patients to use products with scientifically proven benefits leads to better outcomes. Patients should be encouraged to use daily sunscreen, a topical retinoid every night, and a topical antioxidant daily. Supplementing the routine skin care regimen with alpha hydroxy acids, growth factors, heparin sulfate, and defensins can be addressed individually. Exogenous stem cells do not have sufficient evidence to warrant recommending them currently.

Radiofrequency Microneedling
Radiofrequency (RF) skin rejuvenation is improved using RF microneedling (RFM) devices. More aggressive treatments are performed safely with minimal downtime than previous RF devices. Optimizing treatment parameters is essential for safety and efficacy. Multiple RFM studies support minimal risks even in dark skin types. RFM has been used to treat acne scarring successfully as well as skin laxity and hyperhidrosis.

Renuvion/J-Plasma for Subdermal Skin Tightening Facial Contouring and Skin Rejuvenation of the Face and Neck
The Renuvion/J-Plasma helium based plasma device from Apyx Medical has technological features that result in a unique and effective method of action for the contraction of subdermal soft tissue. The device achieves soft tissue contraction by instantly heating tissue to temperatures greater than 85°C for between 0.040 and 0.080 seconds. The tissue surrounding the treatment site remains at much cooler temperatures resulting in rapid cooling of the tissue through conductive heat transfer. Compared to bulk tissue heating devices, this method of action results in effective soft tissue contraction with a lower risk of injury to surrounding tissue.

Advanced Techniques in Nonsurgical Rhinoplasty
For a multitude of reasons, facial plastic surgeons should be adept and comfortable with nonsurgical rhinoplasty. An intimate knowledge of nasal vascular anatomy, filler choice, and proper placement can make this a safe, effective, and long-lasting treatment. Basic techniques include dorsal augmentation and camouflaging of a dorsal hump. Advanced maneuvers are also possible, including increasing tip rotation and projection, straightening the nose, lowering alar rims, and potentially the improvement of nasal function.

The Modified Upper Lip Lift
The modified upper lip lift procedure is a simple evolution of the cutaneous bullhorn subnasal lip lift. The superficial muscular aponeurotic system layer in the lip is described along with the pyriform ligament, both of which play an essential role in lip lifting. This article details an easily reproducible deep-plane technique that can be applied to patients of all ages, ethnicities, and skin types.

Social Media Marketing in Facial Plastic Surgery
Social media is becoming one of the main avenues for direct consumer marketing. Patients use social media to find surgeons and to communicate about procedures, outcomes, and their experiences. A surgeon's social media presence can dramatically increase their perception of being an expert and showcase to patients their style and approach. There is no single best social network, instead various networks exist with unique characteristics that each have the potential to drive traffic to a practice. Social media can be potentially hazardous for patients and surgeons if misused.

A Bioabsorbable Lateral Nasal Wall Stent for Dynamic Nasal Valve Collapse
Nasal obstruction is one of the most common clinical problems encountered by otolaryngologists and facial plastic surgeons. Lateral wall insufficiency (LWI) is a key anatomic contributor to nasal obstruction. Traditional techniques for correcting LWI include alar batten grafts, bone-anchored sutures, and lateral crural strut grafts. Latera is an absorbable nasal implant that can be inserted in the office or the operating room as an adjunctive procedure for LWI. The purpose of this review is to discuss Latera, a novel bioabsorbable implant to improve the nasal airway.

Silhouette Instalift
Absorbable suture suspension is one of the newest minimally invasive treatment trends for lifting and repositioning ptotic facial tissue. The Silhouette Instalift is a convenient in-office procedure that provides a unique and advanced clinical treatment for a natural looking midfacial lift. Research has shown that most patients characterized the Silhouette Instalift as immediately effective and were pleased by enhancements. The procedure has an improved safety and efficacy profile over the predecessor, barbed suture thread lifting, coupled with reduced risk of complications and recovery time compared with rhytidectomy. Absorbable suture suspension should be considered a workhorse in nonsurgical esthetic treatments.

Percutaneous Radiofrequency Technologies for the Lower Face and Neck
The aging neck is one of the most common motivations for patients to seek aesthetic rejuvenation. Increasingly, patients are desiring less invasive aesthetic treatments with less morbidity and downtime. Percutaneous radiofrequency technologies have been recently introduced for cervical rejuvenation. These technologies safely and effectively apply energy directly into the subdermal space, targeting the upper dermal collagen network, the deeper fascial layer, and the fibrofatty septum that anchors the dermis to the deep fascia. Significant skin tightening and fat reduction have been reported with these technologies, beyond that which is currently achievable with other minimally invasive energy-based technologies.

Emerging Trends, Techniques, and Technologies in Facial Plastic and Reconstructive Surgery
Our specialty of Facial Plastic and Reconstructive Surgery is in a period of active and innovative change in technology as well as in techniques. The Facial Plastic Surgery Clinics of North America is pleased to present to our readership this issue, which focuses on those changes as presented by our guest editor, Jason Bloom, MD, and his contributing authors.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Molecular and Cellular Neuroscience

Activation of WNT and CREB signaling pathways in human neuronal cells in response to the Omega-3 fatty acid docosahexaenoic acid (DHA)

Publication date: September 2019

Source: Molecular and Cellular Neuroscience, Volume 99

Author(s): Wen-Ning Zhao, Norma K. Hylton, Jennifer Wang, Peter S. Chindavong, Begum Alural, Iren Kurtser, Aravind Subramanian, Ralph Mazitschek, Roy H. Perlis, Stephen J. Haggarty

Abstract

A subset of individuals with major depressive disorder (MDD) elects treatment with complementary and alternative medicines (CAMs), including the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Previous studies in rodents suggest that DHA modulates neurodevelopmental processes, including adult neurogenesis and neuroplasticity, but the molecular and cellular mechanisms of DHA's potential therapeutic effect in the context of human neurobiology have not been well established. Here we sought to address this knowledge gap by investigating the effects of DHA using human iPSC-derived neural progenitor cells (NPCs) and post-mitotic neurons using pathway-selective reporter genes, multiplexed mRNA expression profiling, and a panel of metabolism-based viability assays. Finally, real-time, live-cell imaging was employed to monitor neurite outgrowth upon DHA treatment. Overall, these studies showed that DHA treatment (0–50 μM) significantly upregulated both WNT and CREB signaling pathways in human neuronal cells in a dose-dependent manner with 2- to 3-fold increases in pathway activation. Additionally, we observed that DHA treatment enhanced survival of iPSC-derived NPCs and differentiation of post-mitotic neurons with live-cell imaging, revealing increased neurite outgrowth with DHA treatment within 24 h. Taken together, this study provides evidence that DHA treatment activates critical pathways regulating neuroplasticity, which may contribute to enhanced neuronal cell viability and neuronal connectivity. The extent to which these pathways represent molecular mechanisms underlying the potential beneficial effects of omega-3 fatty acids in MDD and other brain disorders merits further investigation.

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Modulating proteoglycan receptor PTPσ using intracellular sigma peptide improves remyelination and functional recovery in mice with demyelinated optic chiasm

Publication date: Available online 2 July 2019

Source: Molecular and Cellular Neuroscience

Author(s): Parvin Niknam, Mohammad Reza Raoufy, Yaghoub Fatholahi, Mohammad Javan

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by myelin and axonal damage in the central nervous system (CNS). Glial scar which is a hallmark of MS contains repair inhibitory molecules including chondroitin sulfate proteoglycans (CSPGs). CSPGs inhibit repair of damaged area through various receptors including protein tyrosine phosphatase sigma (PTPσ). In the current study we use intracellular sigma peptide (ISP), an inhibitor of PTPσ signaling, in LPC-induced focal demyelination of mouse optic chiasm. ISP treatment resulted in decreased demyelination, reduced astrogliosis, and increased newly generated oligodendrocytes which subsequently led to enhanced remyelination. Analyzing of electrophysiological (as performed by visual evoked potential recording) and behavioral (performed by visual cliff test) outcomes showed that ISP-treatment improved the integrity of optic pathway as well as the visual acuity. When ISP was administrated only during the repair phase, histological, electrophysiological and behavioral studies showed its regenerative effect. Our results demonstrated the possibility of using ISP as a new strategy to inhibit PTPσ for myelin protection, myelin repair in demyelinated axons, and functional neural pathway conductivity restoration in patients suffering from MS.



Amyloid-beta impairs insulin signaling by accelerating autophagy-lysosomal degradation of LRP-1 and IR-β in blood-brain barrier endothelial cells in vitro and in 3XTg-AD mice

Publication date: Available online 2 July 2019

Source: Molecular and Cellular Neuroscience

Author(s): Chaitanya Chakravarthi Gali, Elham Fanaee-Danesh, Martina Zandl-Lang, Nicole Maria Albrecher, Carmen Tam-Amersdorfer, Anika Stracke, Vinay Sachdev, Florian Reichmann, Yidan Sun, Afrim Avdili, Marielies Reiter, Dagmar Kratky, Peter Holzer, Achim Lass, Karunya K. Kandimalla, Ute Panzenboeck

Abstract

Aberrant insulin signaling constitutes an early change in Alzheimer's disease (AD). Insulin receptors (IR) and low-density lipoprotein receptor-related protein-1 (LRP-1) are expressed in brain capillary endothelial cells (BCEC) forming the blood-brain barrier (BBB). There, insulin may regulate the function of LRP-1 in Aβ clearance from the brain. Changes in IR-β and LRP-1 and insulin signaling at the BBB in AD are not well understood. Herein, we identified a reduction in cerebral and cerebrovascular IR-β levels in 9-month-old male and female 3XTg-AD (PS1M146V, APPSwe, and tauP301L) as compared to NTg mice, which is important in insulin mediated signaling responses. Reduced cerebral IR-β levels corresponded to impaired insulin signaling and LRP-1 levels in brain. Reduced cerebral and cerebrovascular IR-β and LRP-1 levels in 3XTg-AD mice correlated with elevated levels of autophagy marker LC3B. In both genotypes, high-fat diet (HFD) feeding decreased cerebral and hepatic LRP-1 expression and elevated cerebral Aβ burden without affecting cerebrovascular LRP-1 and IR-β levels. In vitro studies using primary porcine (p)BCEC revealed that Aβ peptides 1–40 or 1–42 (240 nM) reduced cellular levels and interaction of LRP-1 and IR-β thereby perturbing insulin-mediated signaling. Further mechanistic investigation revealed that Aβ treatment accelerated the autophagy-lysosomal degradation of IR-β and LRP-1 in pBCEC. LRP-1 silencing in pBCEC decreased IR-β levels through post-translational pathways further deteriorating insulin-mediated responses at the BBB. Our findings indicate that LRP-1 proves important for insulin signaling at the BBB. Cerebral Aβ burden in AD may accelerate LRP-1 and IR-β degradation in BCEC thereby contributing to impaired cerebral and cerebromicrovascular insulin effects.

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mir-234 controls neuropeptide release at the Caenorhabditis elegans neuromuscular junction

Publication date: July 2019

Source: Molecular and Cellular Neuroscience, Volume 98

Author(s): Goda Snieckute, Oguzhan Baltaci, Haowen Liu, Lei Li, Zhitao Hu, Roger Pocock

Abstract

miR-137 is a highly conserved microRNA (miRNA) that is associated with the control of brain function and the etiology of psychiatric disorders including schizophrenia and bipolar disorder. The Caenorhabditis elegansgenome encodes a single miR-137 ortholog called mir-234, the function of which is unknown. Here we show that mir-234 is expressed in a subset of sensory, motor and interneurons in C. elegans. Using a mir-234 deletion strain, we systematically examined the development and function of these neurons in addition to global C. elegans behaviors. We were however unable to detect phenotypes associated with loss of mir-234, possibly due to genetic redundancy. To circumvent this issue, we overexpressed mir-234 in mir-234-expressing neurons to uncover possible phenotypes. We found that mir-234-overexpression endows resistance to the acetylcholinesterase inhibitor aldicarb, suggesting modification of neuromuscular junction (NMJ) function. Further analysis revealed that mir-234 controls neuropeptide levels, therefore positing a cause of NMJ dysfunction. Together, our data suggest that mir-234 functions to control the expression of target genes that are important for neuropeptide maturation and/or transport in C. elegans.

Significance statement

The miR-137 family of miRNAs is linked to the control of brain function in humans. Defective regulation of miR-137 is associated with psychiatric disorders that include schizophrenia and bipolar disorder. Previous studies have revealed that miR-137 is required for the development of dendrites and for controlling the release of fast-acting neurotransmitters. Here, we analyzed the function a miR-137 family member (called mir-234) in the nematode animal model using anatomical, behavioral, electrophysiological and neuropeptide analysis. We reveal for the first time that mir-234/miR-137 is required for the release of slow-acting neuropeptides, which may also be of relevance for controlling human brain function.



Hippocampal sub-regional differences in the microRNA response to forebrain ischemia

Publication date: July 2019

Source: Molecular and Cellular Neuroscience, Volume 98

Author(s): Oiva Arvola, Georgia Kaidonis, Lijun Xu, Brian Griffiths, Creed M. Stary

Abstract

Transient forebrain ischemia, as occurs with cardiac arrest and resuscitation, results in impaired cognitive function secondary to delayed neuronal cell death in hippocampal cornu ammonis-1 (CA1). Comparatively, hippocampal neurons in the adjacent dentate gyrus (DG) survive, suggesting that elucidating the molecular mechanisms underpinning hippocampal sub-regional differences in ischemic tolerance could be central in the development of novel interventions to improve outcome in survivors of forebrain ischemia. MicroRNAs (miRNAs) are non-coding RNAs that modulate the translation of target genes and have been established as an effective therapeutic target for other models of injury. The objective of the present study was to assess and compare post-injury miRNA profiles between CA1 and DG using a rat model of forebrain ischemia. CA1 and DG sub-regions were dissected from rat hippocampi following 10 min of forebrain ischemia at three time points (3 h, 24 h, and 72 h) and at baseline. Pronounced differences between CA1 and DG were observed for several select miRNAs, including miR-181a-5p, a known regulator of cerebral ischemic injury. We complexed fluorescent in situ hybridization with immunohistochemistry to observe cell-type specific and temporal differences in mir-181a-5p expression between CA1 and DG in response to injury. Using established miRNA-mRNA prediction algorithms, we extended our observations in CA1 miRNA dysregulation to identify key functional pathways as potential modulators of CA1 ischemic vulnerability. In summary, our observations support a central role for miRNAs in selective CA1 ischemic vulnerability and suggest that cell-specific miRNA targeting could be a viable clinical approach to preserve CA1 neurons and improve cognitive outcomes for survivors of transient forebrain ischemia.



Acrolein-mediated alpha-synuclein pathology involvement in the early post-injury pathogenesis of mild blast-induced Parkinsonian neurodegeneration

Publication date: July 2019

Source: Molecular and Cellular Neuroscience, Volume 98

Author(s): Glen Acosta, Nicholas Race, Seth Herr, Joseph Fernandez, Jonathan Tang, Edmond Rogers, Riyi Shi

Abstract

Survivors of blast-induced traumatic brain injury (bTBI) have increased susceptibility to Parkinson's disease (PD), characterized by α-synuclein aggregation and the progressive degeneration of nigrostriatal dopaminergic neurons. Using an established bTBI rat model, we evaluated the changes of α-synuclein and tyrosine hydroxylase (TH), known hallmarks of PD, and acrolein, a reactive aldehyde and marker of oxidative stress, with the aim of revealing key pathways leading to PD post-bTBI. Indicated in both animal models of PD and TBI, acrolein is likely a point of pathogenic convergence. Here we show that after a single mild bTBI, acrolein is elevated up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. Acrolein elevation is accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. We further show that acrolein can directly modify and oligomerize α-synuclein in vitro. Taken together, our data suggests acrolein likely plays an important role in inducing PD pathology following bTBI by encouraging α-synuclein aggregation. These results are expected to advance our understanding of the long-term post-bTBI pathological changes leading to the development of PD, and suggest intervention targets to curtail such pathology.



1H NMR profiling of the 6-OHDA parkinsonian rat brain reveals metabolic alterations and signs of recovery after N-acetylcysteine treatment

Publication date: July 2019

Source: Molecular and Cellular Neuroscience, Volume 98

Author(s): Ana Virel, Ilona Dudka, Rutger Laterveer, Sara af Bjerkén

Abstract

Parkinson's disease is the second most common neurodegenerative disease caused by degeneration of dopamine neurons in the substantia nigra. The origin and causes of dopamine neurodegeneration in Parkinson's disease are not well understood but oxidative stress may play an important role in its onset. Much effort has been dedicated to find biomarkers indicative of oxidative stress and neurodegenerative processes in parkinsonian brains. By using proton nuclear magnetic resonance (1H NMR) to identify and quantify key metabolites, it is now possible to elucidate the metabolic pathways affected by pathological conditions like neurodegeneration. The metabolic disturbances in the 6-hydroxydopamine (6-OHDA) hemiparkinsonian rat model were monitored and the nature and size of these metabolic alterations were analyzed. The results indicate that a unilateral injection of 6-OHDA into the striatum causes metabolic changes that not only affect the injected hemisphere but also the contralateral, non-lesioned side. We could clearly identify specific metabolic pathways that were affected, which were mostly related with oxidative stress and neurotransmission. In addition, a partial metabolic recovery by carrying out an antioxidant treatment with N-acetylcysteine (NAC) was observable.



A novel bungarotoxin binding site-tagged construct reveals MAPK-dependent Kv4.2 trafficking

Publication date: July 2019

Source: Molecular and Cellular Neuroscience, Volume 98

Author(s): G. Travis Tabor, Jung M. Park, Jonathan G. Murphy, Jia-Hua Hu, Dax A. Hoffman

Abstract

Kv4.2 voltage-gated K+ channel subunits, the primary source of the somatodendritic A-type K+ current in CA1 pyramidal neurons of the hippocampus, play important roles in regulating dendritic excitability and plasticity. To better study the trafficking and subcellular distribution of Kv4.2, we created and characterized a novel Kv4.2 construct encoding a bungarotoxin binding site in the extracellular S3–S4 linker region of the α-subunit. When expressed, this construct can be visualized in living cells after staining with rhodamine-conjugated bungarotoxin. We validated the utility of this construct by visualizing the spontaneous internalization and insertion of Kv4.2 in HEK 293T cells. We further report that Kv4.2 colocalized with several endosome markers in HEK 293T cells. In addition, Kv4.2 internalization is significantly impaired by mitogen-activated protein kinase (MAPK) inhibitors in transfected primary hippocampal neurons. Therefore, this newly developed BBS-Kv4.2 construct provides a novel and powerful tool for studying surface Kv4.2 channel localization and trafficking.



BDNF elevates the axonal levels of hnRNPs Q and R in cultured rat cortical neurons

Publication date: July 2019

Source: Molecular and Cellular Neuroscience, Volume 98

Author(s): Hui-Wen Chung, Ju-Chen Weng, Chih-En King, Chih-Fan Chuang, Wei-Yuan Chow, Yen-Chung Chang

Abstract

Local translation plays important roles in the maintenance and various functions of axons, and dysfunctions of local translation in axons are implicated in various neurological diseases. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA binding proteins with multiple functions in RNA metabolism. Here, we identified 20 hnRNPs in the axons of cultured rat cortical neurons by interrogating published axon mass spectrometric databases with rat protein databases. Among those identified in axons are highly related hnRNPs Q and R. RT-PCR analysis indicated that axons also contained low levels of hnRNPs Q and R mRNAs. We further found that BDNF treatments raised the levels of hnRNPs Q and R proteins in whole neurons and axons. BDNF also increased the level of poly(A) RNA as well as the proportion of poly(A) RNA granules containing hnRNPs Q and R in the axon. However, following severing the connection between the cell bodies and axons, BDNF did not affect the levels of hnRNPs Q and R, the content of poly(A) RNA, or the colocalization of poly(A) RNA and hnRNPs Q and R in the axon any more, although BDNF still stimulated the local translation in severed axons as it did in intact axons. The results are consistent with that BDNF enhances the axonal transport of RNA granules. The results further suggest that hnRNPs Q and R play a role in the mechanism underlying the enhancement of axonal RNA transport by BDNF.



Mitochondrial dynamics and transport in Alzheimer's disease

Publication date: July 2019

Source: Molecular and Cellular Neuroscience, Volume 98

Author(s): Padraig J. Flannery, Eugenia Trushina

Abstract

Mitochondrial dysfunction is now recognized as a contributing factor to the early pathology of multiple human conditions including neurodegenerative diseases. Mitochondria are signaling organelles with a multitude of functions ranging from energy production to a regulation of cellular metabolism, energy homeostasis, stress response, and cell fate. The success of these complex processes critically depends on the fidelity of mitochondrial dynamics that include the ability of mitochondria to change shape and location in the cell, which is essential for the maintenance of proper function and quality control, particularly in polarized cells such as neurons. This review highlights several aspects of alterations in mitochondrial dynamics in Alzheimer's disease, which may contribute to the etiology of this debilitating condition. We also discuss therapeutic strategies to improve mitochondrial dynamics and function that may provide an alternative approach to failed amyloid-directed interventions.



Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480