Τρίτη 26 Φεβρουαρίου 2019

Effects of combined exercise training in older adults: a potential relationship between muscle fibre satellite cell function and capillarization



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Is prespecification taking the search out of research?



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In this issue: March 2019



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Cover Image

Pediatric Anesthesia Cover Image

The cover image is based on the Research Report Single injection ultrasound‐guided rectus sheath blocks for children: Distribution of injected anesthetic by Mihaela Visoiu et al., DOI: 10.1111/pan.13577.




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Issue Information



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Mechanisms of Fluoroquinolone and Aminoglycoside Resistance in Keratitis-Associated Pseudomonas aeruginosa

Microbial Drug Resistance, Ahead of Print.


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Gaussian-Distributed Codon Frequencies of Genomes

DNA encodes protein primary structure using 64 different codons to specify 20 different amino acids and a stop signal. Frequencies of codon occurrence when ordered in descending sequence provide a global characterization of a genome's preference (bias) for using the different codons of the redundant genetic code. Whereas frequency/rank relations have been described by empirical expressions, here we propose a statistical model in which two different forms of codon usage co-exist in a genome. We investigate whether such a model can account for the range of codon usages observed in a large set of genomes from different taxa. The differences in frequency/rank relations across these genomes can be expressed in a single parameter, the proportion of the two codon compartments. One compartment uses different codons with weak bias according to a Gaussian distribution of frequency, the other uses different codons with strong bias. In prokaryotic genomes both compartments appear to be present in a wide range of proportions, whereas in eukaryotic genomes the compartment with Gaussian distribution tends to dominate. Codon frequencies that are Gaussian-distributed suggest that many evolutionary conditions are involved in shaping weakly-biased codon usage, whereas strong bias in codon usage suggests dominance of few evolutionary conditions.



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Isolation by Distance, Source-Sink Population Dynamics and Dispersal Facilitation by Trade Routes: Impact on Population Genetic Structure of a Stored Grain Pest

Population genetic structure of agricultural pests can be impacted not only by geographic distance and the broader ecological and physical barriers but also by patterns related to where crops are produced and how they are moved after harvest. Stored-product pests, for instance, specialize in exploiting grains such as wheat and rice from on-farm storage through transportation to final processing at often geographically distant locations; therefore human-aided movement may impact their dispersal. Although stored product insects are associated with stored grain, they can also exploit resources in the surrounding environments so different ecological regions where the grain is grown and stored may also influence population structure. Here we used 1,156 SNP markers to investigate how geographic distance, ecological and agricultural variables can impact the genetic structure and gene flow of the stored food pest beetle Rhyzopertha dominica. We found a substantial degree of admixture between weakly structured populations in the US. Ecological regions were more important in explaining R. dominica population structure than crop type, suggesting insect movement between wheat and rice grain distribution channels. We have also found a significant correlation between the genetic and geographical distance (i.e., isolation by distance). However, our modeling approach combining the ecological and management variables has highlighted the importance of the volume of grain received by a location in the dispersal dynamics of the pest. The first-generation migrant analysis offered additional supported to movement over great distances that are likely associated with grain movement. Our data suggest that a multitude of factors play small but significant parts in the movement dynamics of the pest. The beetles can take advantage of the source-sink dynamic of grain movement in the US, but also engage in a high rate of movement at the local scale. Understanding population structure for R. dominica will provide insights into the potential for local processes of adaptation and broader patterns of movement that will impact management programs and the potential for spread of resistance genes.



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The Genetics and Genome-Wide Screening of Regrowth Loci, a Key Component of Perennialism in Zea diploperennis

Perennialism is common among the higher plants, yet little is known about its inheritance. Previous genetic studies of the perennialism in Zea have yielded contradictory results. In this study, we take a reductionist approach by specifically focusing on one trait: regrowth (the plant's ability to restart a new life cycle after senescence on the same body). To address this, six hybrids were made by reciprocally crossing perennial Zea diploperennis Iltis, Doebley & R. Guzman with inbred lines B73 and Mo17 and Rhee Flint, a heirloom variety, of Z. mays L. ssp. mays. All the F1 plants demonstrated several cycles of growth, flowering, senescence and regrowth into normal flowering plants, indicating a dominant effect of the Z. diploperennis alleles. The regrowability (i.e. the plants' ability to regrow after senescence) was stably transmitted to progeny of the hybrids. Segregation ratios of regrowth in the F2 generations are consistent with the trait controlled by two dominant, complementary loci, but do not exclude the influence of other modifiers or environment. Genome-wide screening with genotyping-by-sequencing technology indicated two major regrowth loci, regrowth 1 (reg1) and regrowth 2 (reg2), were on chromosomes 2 and 7, respectively. These findings lay the foundation for further exploration of the molecular mechanism of regrowth in Z. diploperennis. Importantly, our data indicate that there is no major barrier to transferring this trait into maize or other grass crops for perennial crop development with proper technology, which enhances sustainability of grain crop production in an environmentally friendly way.



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Role of motor and cognitive tasks in gait of individuals with mild cognitive impairment

Older adults with mild cognitive impairment (MCI) experience difficulties with memory and task execution. Walking while performing a secondary task could affect gait of individuals with MCI and increase fall risk. The aim of the study was to investigate gait in individuals with MCI performing motor and cognitive secondary tasks. Eight individuals with MCI and eight age-matched healthy older adults walked over the GAITRite walkway under three different conditions: with no secondary task, while carrying a glass of water in their dominant hand (motor task), and while reciting alphabet [cognitive task (CT)]. Gait velocity, cadence, step length, and stride length were calculated. With no secondary task individuals with MCI as compared with the healthy older adults walked slower (P

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Vertebroplasty or kyphoplasty as palliative treatment for cancer-related vertebral compression fractures: a systematic review

Percutaneous vertebroplasty (PVP) and kyphoplasty (KP) are minimally invasive treatment options for VCFs due to malignancy.

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Sequence of acquisition of self-management skills to follow a gluten-free diet by adults with celiac disease

Celiac disease (CD) treatment is lifelong adherence to a gluten-free diet (GFD), requiring mastery of numerous skills to maintain health.

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CHARACTERISTICS AND CONSEQUENCES OF MISSED GASTRIC CANCER: A MULTICENTRIC COHORT STUDY



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Psychophysiological treatment outcomes: Corticotropin‐releasing factor type 1 receptor antagonist increases inhibition of fear‐potentiated startle in PTSD patients

Abstract

After exposure to a traumatic event, a subset of people develop post‐traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear‐potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear‐potentiated startle during a conditional discrimination fear‐conditioning paradigm, termed AX+/BX−. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, double‐blind, placebo‐controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre‐ and 29 post‐treatment) and patients taking a placebo pill (n = 52 pre‐ and 30 post‐treatment) daily for 6 weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre–post‐treatment effect on these measures. However, there was a significant effect of treatment on inhibition of FPS during the AB trials in the AX+/BX− transfer test (p < 0.05). While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post‐treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD.



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Rapid brain responses to affective pictures indicate dimensions of trauma‐related psychopathology in adolescents

Abstract

A variety of mental disorders are related to deviant brain activity, but these neural alterations do not validate psychiatric diagnostic categories. High symptom overlap and variable symptom patterns encourage a dimensional approach. Following the logic of the Research Domain Criteria (RDoC), we investigated trauma survivors for symptom clusters that might be associated with characteristics of ERPs, in particular with the early posterior negativity (EPN) elicited during affective picture processing. In rapid serial visual presentation, 90 adolescents (40 male/50 female, age M = 15.0 ± 2.5 years) who had been exposed to varying amounts of traumatic stress passively viewed a stream of high‐arousing positive and low‐arousing neutral pictures taken from the International Affective Picture System (IAPS). Using standardized interviews, symptoms of trauma‐related mental disorders were assessed (including those for PTSD, depression, borderline personality disorder, and behavioral problems). A principal component analysis was performed to derive potential dimensions of psychopathology. Multiple regression analysis confirmed a factor comprising problems concentrating, sleeping difficulties, and mistrust as a predictor of a larger EPN difference between high‐arousing positive and low‐arousing neutral IAPS pictures (β = 0.19, p < 0.05). Sex predicted the magnitude of the EPN (β = 0.45, p < 0.001). Male adolescents displayed a stronger EPN suppression than female adolescents. The result suggests that problems concentrating, sleeping difficulties, and mistrust seem to be trans‐diagnostic elements related to diminished early emotional discrimination represented by the EPN. Furthermore, our findings indicate that the EPN in response to emotional processing is modulated by sex.



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Temporomandibular pain in adolescents with a history of preterm birth

Abstract

Aim

To evaluate the frequency of TMD pain among adolescents with a history of preterm birth compared to a matched control group.

Methods

A group of 192 preterm‐born adolescents was followed up at the age of 17–19 years and compared to matched controls. Self‐report questionnaires included screening questions about TMD pain, chronic diseases, general health, depression, anxiety, anger, antisocial behavior, and self‐concept. TMD pain was defined as answering 'yes' to one or both of the following questions: "Do you have pain in the temple, face, temporomandibular joint, or jaws once a week or more?" and "Do you have pain when you open your mouth wide or chew once a week or more often?" Data analysis was performed using chi‐square test and logistic regression model with likelihood ratio test.

Results

A TMD pain frequency of 23% of preterm‐born adolescents and 26% among the controls was found, with no significant differences between the groups. Neither were there differences regarding anxiety, depression, anger, or self‐confidence. Within the preterm group, adolescents with TMD pain registered tension and pain in the body, trouble sleeping, stomach pain, and feelings of hopelessness about the future. The controls with TMD pain, more reported having a bad life, feeling like a failure, and having bodily pain. Among tested background variables only TMJ locking or intermittent locking once a week or more was found to explain TMD pain in adolescents.

Conclusion

A high frequency of TMD pain was found in both groups, one possible explanation could be TMJ dysfunction.

This article is protected by copyright. All rights reserved.



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Exercising Caution: Is there a role for exercise testing in the HCM population?



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Epigenomic analysis reveals DNA motifs regulating histone modifications in human and mouse [Genetics]

Histones are modified by enzymes that act in a locus, cell-type, and developmental stage-specific manner. The recruitment of enzymes to chromatin is regulated at multiple levels, including interaction with sequence-specific DNA-binding factors. However, the DNA-binding specificity of the regulatory factors that orchestrate specific histone modifications has not been broadly mapped....

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The ubiquitin ligase UBE3B, disrupted in intellectual disability and absent speech, regulates metabolic pathways by targeting BCKDK [Genetics]

Kaufman oculocerebrofacial syndrome (KOS) is a recessive neurodevelopmental disorder characterized by intellectual disability and lack of speech. KOS is caused by inactivating mutations in UBE3B, but the underlying biological mechanisms are completely unknown. We found that loss of Ube3b in mice resulted in growth retardation, decreased grip strength, and loss...

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Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs [Genetics]

Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes...

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Genetic variant rs17185536 regulates SIM1 gene expression in human brain hypothalamus [Biological Sciences]

Recently in PNAS, Jorgenson et al. (1) conducted a large-scale genome-wide association study (GWAS) to identify genetic variants associated with erectile dysfunction. In the discovery stage, Jorgenson et al. (1) analyze the erectile dysfunction GWAS dataset in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in...

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Reply to Liu et al.: Tissue specificity of SIM1 gene expression and erectile dysfunction [Biological Sciences]

In our study (1), we identify a locus in the human genome near the SIM1 gene that is significantly associated with the risk of erectile dysfunction. Through differential enhancer assays, we demonstrate that the lead single-nucleotide polymorphism (SNP), rs17185536, alters enhancer activity. Furthermore, long-range chromatin interaction experiments show that the...

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A De novo HDAC2 variant in a patient with features consistent with Cornelia de Lange syndrome phenotype

Cornelia de Lange syndrome (CdLS) is an autosomal dominant genetic disorder caused by pathogenic variants in NIPBL, RAD21, SMC3, HDAC8, or SMC1A; all of which code for proteins that are components of, or interact with, the cohesin complex. Despite the identification of multiple genes associated with CdLS, over 25% of individuals strongly suspected to have CdLS have negative genetic testing, indicating that there are additional genes associated with the condition. HDAC2 codes for histone deacetylase 2 (HDAC2) and, like HDAC8, is a Class 1 histone deacetylase. We present a patient with a novel de novo variant in HDAC2 with many clinical features consistent with CdLS including severe developmental delay, limb abnormalities, congenital heart defect, cryptorchidism and hypoplastic genitalia, growth retardation, and characteristic craniofacial features. Although variants in HDAC2 are not currently associated with human disease, the variant identified in this patient is within a highly conserved amino acid residue and has not been observed in healthy populations. This information, along with the patient's clinical presentation and the functional similarity between the HDAC2 and HDAC8 proteins, suggests that HDAC2 should be further investigated as a candidate gene for CdLS or a CdLS‐like syndrome.



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A 2q24.2 microdeletion containing TANK as novel candidate gene for intellectual disability

Interstitial deletions within the chromosomal region 2q24.2 have already been linked to intellectual disability (ID) in the past. In most cases the described patients showed a syndromic form of ID associated with large deletions containing multiple genes. Here we describe a family with two siblings with mild non‐syndromic ID. They shared the same 564 kb deletion in the chromosomal region 2q24.2 containing only the TANK gene, which was inherited from the similarly affected father, thus suggesting haploinsufficiency of TANK as a novel cause of non‐syndromic ID. TANK encodes the TRAF family member‐associated NF‐kappa‐B activator (OMIM #603893), which is expressed in many tissues. It functions as an adapter protein that interacts with the NF‐kappa‐B pathway and SOX11, an essential transcription factor in regeneration, survival and differentiation of the neuronal system. TANK has not been linked to ID or other human diseases before. To further elucidate the role of TANK in non‐syndromic ID, we screened a cohort of 288 TANK deletion negative non‐syndromic mental retardation patients for TANK mutations without identifying any pathogenic variant.



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Exploring by whole exome sequencing patients with initial diagnosis of Rubinstein–Taybi syndrome: the interconnections of epigenetic machinery disorders

Abstract

Rubinstein–Taybi syndrome (RSTS) is an autosomal-dominant neurodevelopmental disease affecting 1:125,000 newborns characterized by intellectual disability, growth retardation, facial dysmorphisms and skeletal abnormalities. RSTS is caused by mutations in genes encoding for writers of the epigenetic machinery: CREBBP (~ 60%) or its homologous EP300 (~ 10%). No causative mutation is identified in up to 30% of patients. We performed whole-exome sequencing (WES) on eight RSTS-like individuals who had normal high-resolution array CGH testing and were CREBBP- and EP300-mutation -negative, to identify the molecular cause. In four cases, we identified putatively causal variants in three genes (ASXL1, KMT2D and KMT2A) encoding members of the epigenetic machinery known to be associated with the Bohring–Opitz, Kabuki and Wiedemann–Steiner syndromes. Each variant is novel, de novo, fulfills the ACMG criteria and is predicted to result in loss-of-function leading to haploinsufficiency of the epi-gene. In two of the remaining cases, homozygous/compound heterozygous variants in XYLT2 and PLCB4 genes, respectively, associated with spondyloocular and auriculocondylar 2 syndromes and in the latter an additional candidate variant in XRN2, a gene yet unrelated to any disease, were detected, but their pathogenicity remains uncertain. These results underscore the broad clinical spectrum of Mendelian disorders of the epigenetic apparatus and the high rate of WES disclosure of the genetic basis in cases which may pose a challenge for phenotype encompassing distinct syndromes. The overlapping features of distinct intellectual disability syndromes reflect common pathogenic molecular mechanisms affecting the complex regulation of balance between open and closed chromatin.



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The impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients: retrospective before-after observational study

Abstract

Purpose

To assess the impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients, we conducted retrospective before-after study in a tertiary teaching hospital.

Methods

We examined all adult patients admitted ICU after an elective operation for head and neck cancer, or esophageal cancer from February 2014 to January 2017. From February 2014 to July 2015, patients were administered hypotonic fluid (sodium; 35 mmol/L) as the National Institute for Health and Care Excellence (NICE) have recommended. From August 2015 to January 2017, patients were administered isotonic fluid (sodium; 140 mmol/L). We defined the incidence of delirium as the primary outcome. The delirium was defined as the Intensive Care Delirium Screening Checklist during the ICU stay ≥ 4. A propensity score-matched model was used to adjust confounders.

Results

As postoperative intravenous maintenance fluid, hypotonic fluid was administered to 119 patients and isotonic fluid was administered to 92 patients. Among those total cohorts, the incidence of postoperative delirium in the hypotonic group was 21.8%, which was significantly higher than that (9.8%) in the isotonic group (p = 0.019). After propensity score matching, we selected 77 patients in each group. The incidence of delirium during the ICU stay in the hypotonic group was 26.0%, which was significantly higher than the incidence of 11.7% in the isotonic group (p = 0.023).

Conclusions

In this study, the use of postoperative hypotonic maintenance fluid was associated with a higher risk of postoperative delirium than that when isotonic maintenance fluid was used.



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Patient satisfaction and clinical outcomes in implant supported overdentures retained by milled bars: Two‐year follow‐up

Abstract

Objectives

This observational clinical study evaluated the patient satisfaction and the clinical outcomes of edentulous arches rehabilitated with overdentures retained by CAD‐CAM milled titanium bars.

Materials and Methods

Edentulous patients were treated with a full‐arch removable overdenture anchored on two milled bars based on a friction retention system. Patient satisfaction was tested using the validated Oral Health Impact Profile (OHIP‐14) questionnaire at the pre‐ and post‐treatment visits, up to two years after prosthesis delivery (possible score range: 0‐56. Best: 0). The prosthodontist satisfaction was also assessed through a designed questionnaire (best possible range 0‐4. Best:0). Radiographic and clinical examinations were performed at baseline and after 2 years of function. Implant and prostheses complications were recorded.

Results

Forty (25 mandible) edentulous patients mean age 69±9.5 (SD) (52% males, 10% smokers), were treated with a total of 187 implants. The mean difference between pre‐ and post‐treatment OHIP‐14 score was 20.6±8.0 (p<0.0001) showing a high level of satisfaction for aesthetics, functional and psychological outcomes. This perception was not influenced by patient's age or gender. The clinicians mean score was 3.4±4.0. There was a marginal bone level (MBL) gain of 0.02±0.22mm between the two time points. Complications were reported in five patients.

Conclusions

This procedure may lead to full satisfaction regarding esthetics and mastication function. One of the most relevant aspects is the versatility, which allows selection of the most suitable treatment option according to patient needs. The prosthodontist satisfaction questionnaire showed that this procedure met the clinical expectations.

This article is protected by copyright. All rights reserved.



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Association between sleep bruxism and anxiety symptoms in adults: a systematic review

Abstract

Background

The purpose of this systematic review was to evaluate the association between sleep bruxism (SB) and anxiety symptoms in adults.

Methods

A systematic review was performed and studies assessing SB by means of questionnaires, clinical examination, and/or polysomnography (PSG), and validated questionnaires to assess anxiety, were included. Search strategies were developed for seven main electronic databases. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross‐Sectional Studies and confidence in cumulative evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation criteria.

Results

Eight cross‐sectional studies were included, of which 5 were judged with low and 3 with moderate risk of bias. No association with SB was observed in 3 studies that investigated generic levels of anxiety, while other 2 papers that evaluated generic anxiety levels through the State‐Trait Anxiety Inventory (STAI) found a positive association with probable and definite SB in both STAI‐1 and STAI‐2 subscales. Only 1 study evaluated dental anxiety in particular and an association with probable SB was observed regarding very anxious or extremely anxious scores. Two studies assessed specific symptoms of anxiety using the panic‐agoraphobic spectra evaluation (PAS‐SR) questionnaire. Significantly higher PAS‐SR total scores were observed in both studies with regard to SB. No study with definitive assessment of SB was identified.

Conclusion

Current literature is controversial regarding an association between SB and generic symptoms of anxiety in adults. It seems that some specific symptoms of the anxiety disorders spectrum might be associated with probable SB.

This article is protected by copyright. All rights reserved.



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Use of illicit amphetamines is associated with long-lasting changes in hand circuitry and control

Publication date: Available online 26 February 2019

Source: Clinical Neurophysiology

Author(s): Verity Pearson-Dennett, Patrick L. Faulkner, Brittany Collie, Robert A. Wilcox, Adam P. Vogel, Dominic Thewlis, Adrian Esterman, Michelle N. McDonnell, Simon C. Gandevia, Jason M. White, Gabrielle Todd

Abstract
Objective

The study aim was to determine if use of illicit amphetamines or ecstasy is associated with abnormal excitability of the corticomotoneuronal pathway and manipulation of novel objects with the hand.

Methods

Three groups of adults aged 18–50 years were investigated: individuals with a history of illicit amphetamine use, individuals with a history of ecstasy use but minimal use of other stimulants, and non-drug users. Transcranial magnetic stimulation was delivered to the motor cortex and the electromyographic response (motor evoked potential; MEP) was recorded from a contralateral hand muscle. Participants also gripped and lifted a novel experimental object consisting of two strain gauges and an accelerometer.

Results

Resting MEP amplitude was larger in the amphetamine group (6M, 6F) than the non-drug and ecstasy groups (p < 0.005) in males but not females. Overestimation of grip force during manipulation of a novel object was observed in the amphetamine group (p = 0.020) but not the ecstasy group.

Conclusions

History of illicit amphetamine use, in particular methamphetamine, is associated with abnormal motor cortical and/or corticomotoneuronal excitability in males and abnormal manipulation of novel objects in both males and females.

Significance

Abnormal excitability and hand function is evident months to years after cessation of illicit amphetamine use.



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Higher Rates of Tuberculosis Among Class B1 Filipino Immigrants to Hawaii Compared to Nationwide, 2010–2014

Abstract

Background

Immigrants to the United States from countries with a high burden of tuberculosis (TB) who have abnormal chest radiographs but negative sputum cultures during pre-immigration screening (TB Class B1) have a high risk of being diagnosed with TB disease within 1 year of arrival.

Methods

Using 2010–2014 national surveillance data, we compared proportions of Class B1 Filipino immigrants who received a diagnosis of TB disease within 1 year of arrival to Hawaii to proportions in other U.S. states (not including Hawaii) using chi-squared tests.

Results

In Hawaii, 40/1190 (3.4%) of Class B1 Filipino immigrants to Hawaii received a diagnosis of TB disease within 1 year of arrival compared with 220/16,035 (1.4%) nationwide (P < .01).

Conclusions

During 2010–2014, the percentage of recent Class B1 Filipino immigrants in Hawaii with TB disease diagnosed within 1 year of arrival was over twice that as nationwide.



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Skeletal Maturation and Predicted Adult Height in Adolescents with Temporomandibular Joint Osteoarthritis

Abstract

Background

The occurrence of osteoarthritis (OA) of the temporomandibular joint (TMJ) in juveniles could be associated with fluctuating levels of estrogen and growth hormone (GH) during adolescence.

Objective

To investigate extent of skeletal maturation and predicted adult height in adolescents with TMJ OA.

Method

In total, 155 adolescents (54 males, 101 females; mean age, 14.1 ± 2.0 years) were enrolled. Among them, 19 adolescents (CON) showed no sign of TMD, 50 adolescents exhibited signs of disc displacement but did not have TMJ OA (TMDnoOA), 23 adolescents exhibited the initial stage of TMJ OA (TMJOAini), and 63 adolescents exhibited the severe stage of TMJ OA (TMJOApro). TMJ OA was diagnosed based on the Research Diagnostic Criteria axis I and bone age was estimated using the Greulich‐Pyle method. The height, weight, and body mass index of participated adolescents were measured and statistically converted to z‐scores. The predicted adult height and age of peak height velocity (APHV) were calculated using the BoneXpert® software.

Results

In female adolescents, the differences between the chronological and bone ages were significantly higher and the z‐score for height was significantly lower in the TMJOApro. Female adolescents with TMJOA exhibited a significantly shorter predicted adult height and earlier APHV than those in the CON and TMDnoOA.

Conclusion

The adolescents with TMJ OA exhibited premature skeletal maturations and short predicted adult stature, particularly the female adolescents.

This article is protected by copyright. All rights reserved.



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The P3b and P600(s): Positive contributions to language comprehension

Abstract

Since its discovery in the 1960s, the P300 has been contributing both directly and indirectly to language research. Perhaps most notably, it has been suggested that the P600, an ERP component that was first characterized in the context of syntactic processing, could be a variant of the P3b subcomponent of the P300. Here, we review studies on both sides of the debate. We also review the "semantic P600," a positivity with a similar time course and distribution to the P600 seen for syntactic manipulations but that is obtained in response to some types of semantic anomalies. Because most current theories of the P600 try to account for both the syntactic and the semantic variant, linking the syntactic P600 to the P3b might also imply a similar link for the semantic P600. However, we describe emerging research in our lab that casts doubt on the idea that the syntactic P600 and the semantic P600 are the same effect. We argue that grouping ERP responses primarily by domain (language vs. nonlanguage) is likely to be misleading and suggest alternative ways of determining whether ERP effects reflect similar or different processing mechanisms.



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Molecular Imaging, vol. 12

  1. 3D Fusion Framework for Infarction and Angiogenesis Analysis in a Myocardial Infarct Minipig Model

    PhD1PhD, MD2MSc1PhD1PhD1PhD2PhD1
    Molecular Imaging, vol. 16First Published May 11, 2017.
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    Abstract

    The combination of different modality images can provide detailed and comprehensive information for the prognostic assessment and therapeutic strategy of patients with ischemic heart disease. In this study, a 3D fusion framework is designed to integrate coronary computed tomography (CT) angiography (CTA), 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) positron emission tomography (PET)/CT, and [68Ga]-1,4,7-triazacyclononane-1,4,7-triacetic acid-(Arg-Gly-Asp)2 ([68Ga]-NOTA-PRGD2) PET/CT images of the myocardial infarction model in minipigs. First, the structural anatomy of the heart in coronary CTA and CT is segmented using a multi-atlas-based method. Then, the hearts are registered using the B-spline-based free form deformation. Finally, the [18F]DG and [68Ga]-NOTA-PRGD2 signals are mapped into the heart in coronary CTA, which produces a single fusion image to delineate both the cardiac structural anatomy and the functional information of myocardial viability and angiogenesis. Heart segmentation demonstrates high accuracy with good agreement between manual delineation and automatic segmentation. The fusion result intuitively reflects the extent of the [18F]DG uptake defect as well as the location where the [68Ga]-NOTA-PRGD2 signal appears. The fusion result verified the occurrence of angiogenesis based on the in vivo noninvasive molecular imaging approach. The presented framework is helpful in facilitating the study of the relationship between infarct territories and blocked coronary arteries as well as angiogenesis.

  2. Open Access

    Whole-Body Distribution of Leukemia and Functional Total Marrow Irradiation Based on FLT-PET and Dual-Energy CT

    Molecular Imaging, vol. 16First Published September 26, 2017.
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    Abstract

    This report describes a multimodal whole-body 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method. Functional total marrow irradiation (fTMI) treatment planning simulations were performed combining FLT-PET and DECT imaging to differentially target irradiation to the leukemia niche and the rest of the skeleton. Leukemia colonized both RM and YM regions, adheres to the cortical bone in the spine, and has enhanced activity in the proximal/distal femur, suggesting a potential association of leukemia with the BME. The planning target volume was reduced significantly in fTMI compared with conventional TMI. The dose to active disease (standardized uptake value >4) was increased by 2-fold, while maintaining doses to critical organs similar to those in conventional TMI. In conclusion, a hybrid system of functional–anatomical–physiological imaging can identify the spatial distribution of leukemia and will be useful to both help understand the leukemia niche and develop targeted radiation strategies.

  3. Open Access

    Vulnerable Plaque Detection and Quantification with Gold Particle–Enhanced Computed Tomography in Atherosclerotic Mouse Models

    Molecular Imaging, vol. 14, 6First Published June 1, 2015.
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    Abstract

    Recently, an apolipoprotein E–deficient (ApoE−/−) mouse model with a mutation (C1039G+/−) in the fibrillin-1 (Fbn1) gene (ApoE−/−Fbn1C1039G+/− mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE−/− mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle–enhanced micro–computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE−/−Fbn1C1039G+/− compared to the ApoE−/−mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle–enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.

  4. Open Access

    Complementary Use of Bioluminescence Imaging and Contrast-Enhanced Micro—Computed Tomography in an Orthotopic Brain Tumor Model

    Molecular Imaging, vol. 13, 4First Published January 1, 2015.
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    Abstract

    Small animal models are crucial to link molecular discoveries and implementation of clinically relevant therapeutics in oncology. Using these models requires noninvasive imaging techniques to monitor disease progression and therapy response. Micro–computed tomography (CT) is less studied for the in vivo monitoring of murine intracranial tumors and traditionally suffers from poor soft tissue contrast, whereas bioluminescence imaging (BLI) is known for its sensitivity but is not frequently employed for quantifying tumor volume. A widely used orthotopic glioblastoma multiforme (GBM) tumor model was applied in nude mice, and tumor growth was evaluated by BLI and contrast-enhanced microCT imaging. A strong correlation was observed between CT volume and BLI-integrated intensity (Pearson coefficient (r) = .85, p = .0002). Repeated contouring of contrast-enhanced microCT-delineated tumor volumes achieved an intraobserver average pairwise overlap ratio of 0.84 and an average tumor volume coefficient of variance of 0.11. MicroCT-delineated tumor size was found to correlate with tumor size obtained via histologic analysis (Pearson coefficient (r) = .88, p = .005). We conclude that BLI intensity can be used to derive tumor volume but that the use of both contrast-enhanced microCT and BLI provides complementary tumor growth information, which is particularly useful for modern small animal irradiation devices that make use of microCT and BLI for treatment planning, targeting, and monitoring.

  5. Free Access

    Development and Validation of a Complete GATE Model of the Siemens Inveon Trimodal Imaging Platform

    Molecular Imaging, vol. 12, 7First Published October 1, 2013.
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    Abstract

    This article presents and validates a newly developed GATE model of the Siemens Inveon trimodal imaging platform. Fully incorporating the positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) data acquisition subsystems, this model enables feasibility studies of new imaging applications, the development of reconstruction and correction algorithms, and the creation of a baseline against which experimental results for real data can be compared. Model validation was based on comparing simulation results against both empirical and published data. The PET modality was validated using the NEMA NU-4 standard. Validations of SPECT and CT modalities were based on assessment of model accuracy compared to published and empirical data on the platform. Validation results show good agreement between simulation and empirical data of approximately ± 5%.

  6. Free Access

    Use of eXIA 160 XL for Contrast Studies in Micro–Computed Tomography: Experimental Observations

    Molecular Imaging, vol. 12, 6First Published September 1, 2013.
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    Abstract

    The purpose of this study was to evaluate the time course of contrast enhancement of spleen, liver, and blood using eXIA 160 XL in healthy mice. eXIA 160 XL was intravenously injected in C57bl/6 mice (n = 12) at a dose of 0.1 mL/20 g (16 mg iodine [I]/20 g) (n = 6) or 0.2 mL/20 g (32 mg I/20 g) (n = 6). The distribution was analyzed by repeated micro–computed tomographic scans up to 48 hours after contrast administration. Images were analyzed using Amidesoftware. Regions of interest were drawn in the spleen, liver, and left ventricle. Contrast enhancement was measured and expressed as a function of time. Peak contrast enhancement of the spleen was reached at 30 minutes, and peak contrast enhancement of the liver occurred 45 minutes after 16 mg I/20 g. Given that this contrast was found to be rather low in the spleen in comparison with former eXIA 160 products, experiments were done at a higher dose. However, the 32 mg I/20 g dose was lethal for mice. Enhancement inside the heart lasts for 1 hour. Administration of eXIA 160 XL results in long-lasting blood pool contrast with higher contrast enhancement in heart and liver in comparison with eXIA 160; however, the administered dose should be limited to 16 mg I/20 g.

  7. Free Access

    Comparison of Computed Tomography– and Optical Image–Based Assessment of Liposome Distribution

    Molecular Imaging, vol. 12, 3First Published May 1, 2013.
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    Abstract

    The use of multimodal imaging as a tool to assess the in vivo pharmacokinetics and biodistribution of nanocarriers is important in understanding the nature of their in vivo transport. The current study reports the development of a nano-sized liposomal computed tomographic (CT)/optical imaging probe carrying iohexol and Cy5.5 and its use in micro-CT and optical imaging to quantitatively assess the whole-body (macroscopic), intratumoral, and microscopic distribution over a period of 8 days. These multimodal liposomes have a vascular half-life of 30.3 ± 8.9 hours in mice bearing subcutaneous H520 non-small cell lung cancer tumors, with the maximum liposome accumulation in tumor achieved 48 hours postinjection. The in vivo liposome distribution and stability were quantitatively assessed using both micro-CT and fluorescence molecular tomography. The combination of CT and optical imaging enables visualization of the liposomes at the whole-body, tumor, and cellular scales with high sensitivity. Such noninvasive tracking of therapeutic vehicles at the macro- and microscale is important for informed and rational development of novel nanocarrier systems.