Further characterization of CAPOS/CAOS syndrome with the Glu818Lys mutation in the ATP1A3 gene: A case report

Publication date: Available online 3 April 2018
Source:Brain and Development
Author(s): Takuya Hayashida, Yoshiaki Saito, Atsushi Ishii, Shinichi Hirose, Rika Hiraiwa, Yoshihiro Maegaki, Kousaku Ohno
A 38-year-old female patient experienced recurrent episodes of neurological deterioration during febrile illness at the age of 7 and 8 months, and 2, 4, and 37 years. Acute symptoms comprised unconsciousness, headache, abnormal ocular movements, flaccid paralysis with areflexia, ataxia, dysphagia, and movement disorders. Each episode of neurological deterioration was followed by partial recovery with residual symptoms of progressive disturbance of visual acuity with optic atrophy and hearing loss, moderate intellectual disability, strabismus, ophthalmoplegia, as well as fluctuating degree of gait ataxia, chorea, tremor, and myoclonus. In addition, electrocardiography revealed incomplete right bundle branch block. The genetic testing revealed a de novo heterozygous mutation of c.2452G > A (p.Glu818Lys) in the ATP1A3 gene, which was compatible with the clinical phenotype of CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss)/CAOS syndrome. Here we discuss the significance of clinical features of a patient, overlapping with those of alternating hemiplegia of childhood, along with a literature review.



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Effectiveness of total corpus callosotomy for diffuse bilateral polymicrogyria: Report of three pediatric cases

Publication date: Available online 3 April 2018
Source:Brain and Development
Author(s): Shimpei Baba, Tohru Okanishi, Mitsuyo Nishimura, Sotaro Kanai, Shinji Itamura, Takayuki Suzuki, Yosuke Masuda, Hideo Enoki, Ayataka Fujimoto
PurposePolymicrogyria, a malformation of the cerebral cortex, frequently causes epilepsy. Diffuse bilateral polymicrogyria (DBP) is related to poor epilepsy prognosis, but most patients with DBP are not good candidates for resective epilepsy surgery and effectiveness of corpus callosotomy (CC), a palliative surgery, for patients without resective epileptogenic cortices, has not been established in DBP. Because CC might be effective against DBP-related epilepsy, we conducted total CC in three pediatric DBP cases.MethodsCase 1. A girl developed epilepsy at 3 months of age, with focal versive seizures and epileptic spasms. The electroencephalogram (EEG) showed a suppression-burst pattern. Total CC was performed at 6 months of age.Case 2. A female infant developed epilepsy on the day of birth, exhibiting epileptic spasms, generalized tonic-clonic seizures, and eye-deviating seizures. She had a history of clusters of tonic seizures. Total CC was performed at 1 year and 2 months of age. After CC, the epileptic focus of the tonic seizures was identified; a secondary resective surgery was conducted.Case 3. A girl developed multiple types of seizures at 3 years of age. Frequent atypical absence status was refractory to antiepileptic drugs. Total CC was conducted at 8 years of age.ResultsCase 1: Frequencies of both seizure types decreased. The background EEG changed to continuous high-voltage slow waves.Case 2: Clusters of tonic seizures were well-controlled.Case 3: Atypical absence seizures completely disappeared.ConclusionCC could be effective for patients with DBP, whose habitual seizures include epileptic spasms and absence seizures.



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The Eyes Reveal Uncertainty about Object Distinctions in Semantic Variant Primary Progressive Aphasia

Publication date: Available online 3 April 2018
Source:Cortex
Author(s): Andreia V. Faria, David Race, Kevin Kim, Argye E. Hillis
At least three distinct variants of primary progressive aphasia (PPA) have been described, but they are difficult to distinguish early in the course, when individuals experience primarily anomia. People with svPPA are often the hardest to care for, because they have impaired comprehension of words and objects and often have negative changes in comportment. We sought to identify an early marker of semantic variant primary progressive aphasia (svPPA) and to enhance the understanding of the semantic deficit in svPPA. We hypothesized that the pattern of eye tracking in a word picture matching task can differentiate svPPA from other variants and can predict which participants with unclassifiable PPA will progress to svPPA. We tested 19 individuals with PPA on a word picture matching task with eye tracking. We found that individuals with svPPA were less accurate than other variants when the foils were semantic coordinates (horse-cow) or schematically related (horse-saddle), but not when they were thematically related (saw-horse) or unrelated. Moreover, even in the condition in which they were highly accurate (unrelated foils) they looked much more often to the foils and for longer, than other variants or controls. Unclassifiable PPA participants who eventually developed svPPA showed the same pattern. This abnormal pattern was associated with atrophy in bilateral temporal poles.



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C5a receptor1 inhibition alleviates influenza virus-induced acute lung injury

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Nianping Song, Pei Li, Yuting Jiang, Hong Sun, Jing Cui, Guangyu Zhao, Dan Li, Yan Guo, Yuehong Chen, Jimin Gao, Shihui Sun, Yusen Zhou
Influenza A virus is an important human pathogen that causes 3 to 5 million severe cases of influenza worldwide each year. An aberrant innate immune response, particularly hypercytokinemia, is thought to play an important role in the disease, although the pathogenesis of severe influenza virus infection remains unclear and no specific and efficacious immunotherapy is available. This study reports dysregulated complement activation in mice after infection with A/Puerto Rico/8/34 (PR8). C5aR1-deficient mice and mice treated with an anti-C5aR1 antibody were used as models to study the C5a-C5aR1 axis during acute lung injury (ALI) induced by influenza virus infection. The results showed that blocking the C5a-C5aR1 axis alleviated ALI by inhibiting endothelial cell activation and dampening the host immune response (i.e., reduced TNF-α, IL-1β, IL-6, IP-10, MCP-1, IL-12p70, and IFN-γ concentrations in plasma), particularly CTL-mediated immunopathology. Furthermore, blockade of the C5a-C5aR1 axis inhibited viral replication in lung tissue. Taken together, the results indicate that the C5a-C5aR1 axis plays an important role in the outcome of ALI induced by influenza virus infection and that regulation of complement activation, particularly the C5aR1 inhibition, is a promising intervention and adjunctive treatment.



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20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Yan-dan Zhou, Jin-gang Hou, Wei Liu, Shen Ren, Ying-ping Wang, Rui Zhang, Chen Chen, Zi Wang, Wei Li
Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, thein vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20(R)-Ginsenoside Rg3 (20(R)-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20(R)-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20(R)-Rg3 pretreatment. Moreover, 20(R)-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20(R)-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20(R)-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage.



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Protective effect of pristimerin against LPS-induced acute lung injury in mice

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Ahmed A. Shaaban, Dalia H. El-Kashef, Mohamed F. Hamed, Dina S. El-Agamy
Pristimerin (Pris) is a triterpenoid derivative obtained from Celastraceae and Hippocrateaceae families. This compound has been extensively tested for its potent anti-cancer activity against different types of tumors. However, its effects against acute lung injury (ALI) remain to be investigated. This study explored the efficacy of Pris to protect against lipopolysaccharide (LPS)-induced ALI and its possible pathways. Results have shown that Pris possesses potent protective activity against LPS-induced acute lung damage. It significantly decreased pulmonary edema as presented by significant decrease in lung W/D ratio and in protein content. Pris attenuated LPS-induced inflammatory cell infiltration into the lung tissue and suppressed the activity of myeloperoxidase in lung. LPS-induced histopathological lesions were significantly improved via Pris pretreatment. Pris exhibited not only inhibition of LPS-induced oxidative stress, but also enhancement of the suppressed antioxidant capacity of the lung tissue. The anti-inflammatory activity of Pris against LPS-induced ALI was clearly evident via attenuation of the levels of pro-inflammatory cytokines namely, tumor necrosis factor-α and interleukin-6. Similarly, Pris inhibited LPS-induced elevation of pro-apoptotic protein, Bax, and caspase-3. Pris also increased the diminished level of Bcl2 induced by LPS. Collectively, Pris exerted protective activity against LPS-induced ALI via anti-oxidant, anti-inflammatory and anti-apoptotic pathways.



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JMJD3 is involved in neutrophil membrane proteinase 3 overexpression during the hyperinflammatory response in early sepsis

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Yang Chen, Zhaojun Liu, Tingting Pan, Erzhen Chen, Enqiang Mao, Ying Chen, Ruoming Tan, Xiaoli Wang, Rui Tian, Jialin Liu, Hongping Qu
Excessive production of pro-inflammatory cytokines in early sepsis causes high early mortality rates. Membrane proteinase 3 (mPR3) expression on neutrophils plays a critical role in pro-inflammatory cytokine production. However, the mechanism underlying mPR3 overexpression in early sepsis is unknown. Here, we explored mPR3 expression in early sepsis and its regulatory mechanism. Thirty-two patients with sepsis and 20 healthy controls were prospectively enrolled. On day 1 after the onset of sepsis, mPR3 and jumonji domain-containing protein D3 (JMJD3) expression levels were measured in peripheral blood neutrophils. Lipopolysaccharide (LPS) was employed to induce JMJD3 expression in vitro, and GSK-J4 was used to inhibit JMJD3. Neutrophils were divided into four groups, control, LPS, LPS + GSK-J4, and GSK-J4, and cultured with THP-1 cells respectively. Plasma and culture supernatant cytokine levels were measured by enzyme-linked immunosorbent assays. Neutrophil mPR3 levels were significantly higher in patients with early sepsis than in healthy controls. Plasma cytokine (IL-1β and TNF-α) levels were increased in patients with sepsis exhibiting high mPR3 expression. Additionally, JMJD3 expression levels in neutrophils were increased in early sepsis. In vitro, both mPR3 on neutrophils and IL-1β in culture supernatants increased in response to LPS stimulation. Neutrophil mPR3 expression and IL-1β levels were significantly reduced by GSK-J4 in cells treated with LPS. IL-1β level was significantly higher in LPS-stimulated co-culture supernatants than in the corresponding individual cultured cells. Thus, our results suggest that JMJD3 contributes to the high expression of neutrophil mPR3, which promotes the production of proinflammatory IL-1β in early sepsis.



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Antiviral activity of porcine interferon delta 8 against foot-and-mouth disease virus in vitro

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Shi-fang Li, Jun-jun Shao, Fu-rong Zhao, Mei-jiao Gong, Yin-li Xie, Hui-yun Chang, Yong-guang Zhang
Foot-and-mouth disease (FMD) is one of the most devastating diseases affecting livestock. Since vaccines fail to provide protection until seven days post-vaccination, the application of anti-viral molecules is imperative for suppressing the spread of FMDV prior to development of an adaptive immune response. Interferons (IFNs) are effective for the host to fight FMDV infections; however, a novel type I IFNs, interferon delta (IFN-δ), has not been investigated for their antiviral effects against this virus. Thus, this study investigated FMDV infection, upon pre- and post-treatment with PoIFN-δ8. Real-time quantitative PCR was used to quantify the expression levels of IFN-stimulated genes (ISGs), including ISG15, OAS1, PKR, and Mx1. Results showed the PoIFN-δ8 lacking its signal sequence was efficiently expressed in Escherichia coli, and the purified recombinant PoIFN-δ8 exerted a significantly protective effect against two different serotypes of FMDV in IBRS-2 cells. In addition, PoIFN-δ8 induced the expression of IFN-stimulated genes. These findings highlight the significance of PoIFN-δ might serve as an antiviral agent for the prevention of FMDV in pigs and will stimulate the study of exploiting the potential biological functions of IFN-δ in the future.



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Dysfunction of regulatory T cells in patients with ankylosing spondylitis is associated with a loss of Tim-3

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Mingfei Wang, Chengyi Liu, Allen Bond, Jun Yang, Xu Zhou, Jian Wang, Bin Ji
An expansion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) was observed. However, AS patients continue to exhibit aberrant inflammation. In this study, we collected PBMCs from 26 AS patients and 26 healthy controls, and investigated the functional capacity of Treg cells from these subjects. In AS patients, the frequency of CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells was slightly increased compared to healthy controls, but the level of Foxp3 MFI in AS patient CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells was significantly lower than that in healthy control CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells. Tim-3⁺ Treg cells were previously shown to present stronger suppressive capacity than Tim-3⁻ Treg cells. Here, we discovered that the Tim-3⁺ cell frequency in CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells was significantly lower in AS patients. In both healthy volunteers and AS patients, Tim-3⁺ Treg cells demonstrated higher transcription of Foxp3, IL-10 and TGF-β, higher secretion of IL-10 and TGF-β, and stronger inhibition of conventional T cell inflammation, than Tim-3⁻ Treg cells. In some but not all functional aspects, the Tim-3⁺ Treg cells from healthy controls were more potent than the Tim-3⁺ Treg cells from AS patients. Collectively, these results demonstrated two Treg-related impairments in AS patients. First, the frequency of the more potent Tim-3⁺ Treg cells was lower in AS patients, and second, some of Tim-3⁺ Treg-mediated functions were less potent in AS patients. Interestingly, the ratio of Tim-3⁻/Tim-3⁺ Treg cells in AS patients was directly correlated with the Bath ankylosing spondylitis disease activity index (BASDAI) score, the C-reactive protein (CRP) level, and the erythrocyte sedimentation rate (ESR). Given the fact that Tim-3⁺ Treg cells presented potent suppressive functions, Tim-3⁺ Treg cells and Tim-3⁺ Treg-mediated mechanisms might be potential candidates for immunotherapies in AS patients.



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Targeting macrophage immunometabolism: Dawn in the darkness of sepsis

Publication date: May 2018
Source:International Immunopharmacology, Volume 58
Author(s): V. Kumar
Sepsis is known since the time (470 BC) of great Greek physician, Hippocrates. Advancement in modern medicine and establishment of separate branches of medical science dealing with sepsis research have improved its outcome. However, mortality associated with sepsis still remains higher (25–30%) that further increases to 40–50% in the presence of septic shock. For example, sepsis-associated deaths account more in comparison to deaths-associated with myocardial-infarction and certain cancers (i.e. breast and colorectal cancer). However, it is now well established that profound activation of innate immune cells including macrophages play a very important role in the immunopathogenesis of sepsis. Macrophages are sentinel cells of the innate immune system with their location varying from peripheral blood to various target organs including lungs, liver, brain, kidneys, skin, testes, vascular endothelium etc. Thus, profound and dysregulated activation of these cells during sepsis can directly impact the outcome of sepsis. However, the emergence of the concept of immunometabolism as a major controller of immune response has raised a new hope for identifying new targets for immunomodulatory therapeutic approaches. Thus this present review starts with an introduction of sepsis as a major medical problem worldwide and signifies the role of dysregulated innate immune response including macrophages in its immunopathogenesis. Thereafter, subsequent sections describe changes in immunometabolic stage of macrophages (both M1 and M2) during sepsis. The article ends with the discussion of novel macrophage-specific therapeutic targets targeting their immunometabolism during sepsis and epigenetic regulation of macrophage immunometabolism and vice versa.

Graphical abstract

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Predictive Validity of the STarT Back Tool for Risk of Persistent Disabling Back Pain in a United States Primary Care Setting

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Pradeep Suri, Kristin Delaney, Sean D. Rundell, Daniel C. Cherkin
ObjectiveTo examine the predictive validity of the STarT Back tool for classifying people with back pain into categories of low, medium, and high risk of persistent disabling back pain, in US primary care.DesignSecondary analysis of data from participants receiving usual care in a randomized clinical trial.SettingPrimary care clinics.Participants1109 adults with back pain ≥18 years of age. Those with specific causes of back pain (pregnancy, disc herniation, vertebral fracture, spinal stenosis) and work-related injuries were not included.InterventionsN/AMain Outcome MeasuresThe original 9-item version of the STarT Back tool, administered at baseline, stratified patients by their risk (low, medium, high) of persistent disabling back pain ('STarT Back risk group'). Persistent disabling back pain was defined as Roland-Morris Disability Questionnaire scores of ≥7 at 6-month follow-up.ResultsSTarT Back risk group was a significant predictor of persistent disabling back pain (p<0.0001) at 6-month follow-up. The proportion of individuals with persistent disabling back pain at follow-up was 22% (95% confidence interval [CI] 18-25%) in the low risk group, 62% (95% CI 57-67%) in the medium-risk group, and 80% (95% CI 75-85%) in the high-risk group. The relative risk of persistent disabling back pain was 2.9 (95% CI 2.4-3.5) in the medium-risk group as compared to the low-risk group, and 3.7 (95% CI 3.1-4.4) in the high-risk group.ConclusionsWe found that the STarT Back risk groups successfully separated people with back pain into distinct categories of risk for persistent disabling back pain at 6-month follow-up in US primary care. These results were very similar to those seen in the original STarT Back validation study. This validation study is a necessary first step towards identifying whether the entire STarT Back approach, including matched/targeted treatment, can be effectively used for primary care in the US.



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Conceptual Underpinnings of the Quality of Life in Neurological Disorders (Neuro-QoL): Comparisons of Core Sets for Stroke, Multiple Sclerosis, Spinal Cord Injury, and Traumatic Brain Injury

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Alex W.K. Wong, Stephen C.L. Lau, Mandy W.M. Fong, David Cella, Jin-Shei Lai, Allen W. Heinemann
ObjectiveTo determine the extent to which the content of the Quality of Life in Neurological Disorders (Neuro-QoL) covers the ICF core sets for multiple sclerosis (MS), stroke, spinal cord injury (SCI), and traumatic brain injury (TBI) using summary linkage indicators.DesignContent analysis by linking content of the Neuro-QoL to corresponding ICF codes of each core set for MS, stroke, SCI, and TBI.SettingThree academic centersParticipantsNoneInterventionsNoneMain Outcome MeasureFour summary linkage indicators proposed by MacDermid and colleagues were estimated to compare the content coverage between Neuro-QoL and the ICF codes of core sets for MS, stroke, MS, and TBI.ResultsNeuro-QoL represented 20%-30% core set codes for different conditions in which more codes in core sets for MS (29%), stroke (28%), and TBI (28%) were covered than those for SCI in the LT (20%) and EPA (19%) contexts. Neuro-QoL represented nearly half of the unique Activity and Participation codes (43%–49%) and less than one-third of the unique Body Function codes (12%−32%). It represented fewer environmental codes (2%−6%) and no Body Structures codes. Absolute linkage indicators found that at least 60% of Neuro-QoL items were linked to core set codes (63%-95%) but many items covered same codes as revealed by unique linkage indicators (7%-13%), suggesting high concept redundancy among items.ConclusionThe Neuro-QoL links more closely to ICF core sets for stroke, MS, and TBI than to those for SCI, and primarily covers Activity and Participation ICF domains. Other instruments are needed to address concepts not measured by the Neuro-QoL when a comprehensive health assessment is needed.



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Measurement Characteristics and Clinical Utility of the Pediatric Evaluation of Disability Inventory in Children With Cerebral Palsy

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Sarah Brew, Erin Langan, Amanda Link-Dudek, Ryan Walsh, Linda Ehrlich-Jones




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Effectiveness of Client-Centered “Tune-Ups” on Community Reintegration, Mobility, and Quality of Life After Stroke: A Randomized Controlled Trial

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Brenda Brouwer, Dianne Bryant, S. Jayne Garland
ObjectiveTo explore the effectiveness of a 2-week client-centered rehabilitation intervention (tune-up) delivered 6 months after inpatient discharge on community reintegration at 1 year in people with stroke.DesignA multicenter randomized controlled trial with 2 groups: an intervention ("tune-up") group and a control group having the same exposure to assessment.SettingThree research laboratories.ParticipantsParticipants (N=103) with hemiparetic stroke recruited from inpatient rehabilitation units at the time of discharge.InterventionsParticipants randomized to the tune-up group received 1-hour therapy sessions in their home 3times/wk for 2 weeks at 6 months postdischarge focusing on identified mobility-related goals. A second tune-up was provided at 12 months.Main Outcome MeasuresCommunity reintegration measured by the Subjective Index of Physical and Social Outcome at 12 months and secondary outcomes included the Berg Balance Scale and measures of mobility and health-related quality of life up to 15 months.ResultsAt 12 months, both groups showed significant improvement in community reintegration (P<.05), a trend evident at all time points, with no difference between groups (mean difference, −0.5; 95% confidence interval, −1.8 to 2.7; P=.68). Similarly, a main effect of time reflected improvement in mobility-related and quality of life outcomes for both groups (P≤.0.5), but no group differences (P≥.30).ConclusionsAll participants in the tune-up group met or exceeded at least 1 mobility-related goal; however, the intervention did not differentially improve community reintegration. The improvements in mobility and quality of life over the 15-month postdischarge period may be secondary to high activity levels in both study groups and exposure to regular assessment.



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Is going beyond Rasch analysis necessary to assess the construct validity of a motor function scale?

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Tiffanie Guillot, Sylvain Roche, Pascal Rippert, Dalil Hamroun, Jean Iwaz, René Ecochard, Carole Vuillerot
ObjectiveExamine whether a Rasch analysis is sufficient to establish the construct validity of the Motor Function Measure (MFM) and discuss whether weighting the MFM item scores would improve the MFM construct validity.DesignObservational cross-sectional multicenter study.Setting23 physical medicine departments, neurology departments, or reference centers for neuromuscular diseasesParticipants911 patients (aged 6 to 60 years) with Charcot-Marie-Tooth disease (CMT), facio-scapulo-humeral dystrophy (FSHD), or myotonic dystrophy type 1 (DM1)InterventionsNone.Main Outcome Measure(s)Comparison of the goodness-of-fit of the Confirmatory Factor Analysis (CFA) model vs. that of a modified multidimensional Rasch model on MFM item scores in each considered disease.ResultsCFA model showed good fit to the data and significantly better goodness-of-fit than the modified multidimensional Rasch model whatever the disease (P<0.001). Statistically significant differences in item standardized factor loadings were found between DM1, CMT, and FSHD in only 6 out of 32 items (Items 6, 27, 2, 7, 9 and 17).ConclusionIn the case of multidimensional scales designed to measure patient abilities in various diseases, a Rasch analysis might not be the most convenient whereas a CFA is able to establish the scale construct validity and provide weights to adapt the item scores to a specific disease.



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Contribution to the understanding of biologic concentrations of arsenic in children living in an urban area from Rio de Janeiro, Brazil

Abstract

There are few studies about children's environmental exposure to arsenic (As) in Brazil, most of them being in mining regions. The objective of this study was to contribute to the understanding of biologic concentrations of arsenic in children living in an urban area, in Brazil. A study of arsenic concentrations in capillary blood (n = 270), nail (n = 261), and urine (n = 99) samples, in male and female children, 8 to 10 years old, from two public schools in Rio de Janeiro, was conducted. Socio-economic and health data were obtained through questionnaires. The nail and capillary blood analysis were performed by inductively coupled plasma mass spectrometry (ICP-MS), while urine samples were analyzed using hydride generation atomic absorption spectrometry (HG-AAS). The median, geometric mean, and 95th percentiles of total arsenic concentrations were, respectively, 2.53, 2.40, and 3.58 μg/L in capillary blood; 0.09, 0.10, and 0.24 μg/g in nails; and 12.50, 10.97, and 39.45 μg/L in urine. The geometric mean of urinary arsenic level was above the values reported by international surveys for non-exposed populations. The arsenic concentrations in nails were compatible with the values found in national studies. These outcomes can contribute to the increase of knowledge on biologic concentrations of arsenic in children living in urban areas, in Brazil.

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Characterization of toluene metabolism by methanotroph and its effect on methane oxidation

Abstract

Methanotrophs not only oxidize CH₄, but also can oxidize a relatively broad range of other substrates, including trichloroethylene, alkanes, alkenes, and aromatic compounds. In this study, Methylosinus sporium was used as a model organism to characterize toluene metabolism by methanotrophs. Reverse transcription quantitative PCR analysis showed that toluene enhanced the mmoX expression of M. sporium. When the toluene concentration was below 2000 mg m⁻³, the kinetics of toluene metabolism by M. sporium conformed to the Michaelis-Menten equation (V_max = 0.238 g g_{dry weight}⁻¹ h⁻¹, K_m  = 545.2 mg m⁻³). The use of a solid-phase extraction technique followed by a gas chromatography-mass spectrometry analysis and molecular docking calculation showed that toluene was likely to primarily bind the di-iron center structural region of soluble methane monooxygenase (sMMO) hydroxylase and then be oxidized to o-cresol. Although M. sporium oxidized toluene, it did not incorporate toluene into its biomass. The coexistence of toluene and CH₄ could influence CH₄ oxidation, the growth of methanotrophs, and the distribution of CH₄-derived carbon, which were related to the ratio of the toluene concentration to biomass. These results would be helpful to understand the metabolism of CH₄ and non-methane volatile organic compounds in the environment.

https://ift.tt/2GQBM92

Politically-focused intrusive thoughts and associated ritualistic behaviors in a community sample

Publication date: Available online 31 March 2018
Source:Journal of Anxiety Disorders
Author(s): Sandra L. Cepeda, Dean McKay, Sophie C. Schneider, Valérie La Buissonnière-Ariza, Egberts Jolenthe T.N.E., Elizabeth McIngvale, Wayne K. Goodman, Eric A. Storch
A significant proportion of the U.S. population report increased stress attributed to the political climate following the controversial 2016 United States (U.S.) Presidential election. The political stressors paired with the growth in news consumption and social media-use could be a potential trigger for obsessive-compulsive-like symptoms specific to politics in some individuals. This study aimed to elucidate the rate of Politically-focused Intrusive Thoughts and associated Ritualistic Behaviors (PITRB), their demographic and clinical correlates, and the degree of association with political ideology. Survey data were collected using the crowdsourcing platform Mechanical Turk. A total of N = 484 individuals completed the survey. Measures of politically-focused intrusive thoughts and ritualistic behaviors, general obsessive-compulsive symptoms, depression, anxiety, anxiety control, worry, and disability were administered, as well as a measure of social and economic conservative affiliation. Results showed that a quarter of the sample (25.2%) had at least one PITRB more than once a day. PITRB was associated with all measures of psychopathology and disability. Finally, anxiety control moderated the relationship between PITRB and both anxiety and depression. No differences in psychopathology were found between major party affiliations. The findings suggest that politically-focused intrusive thoughts and ritualistic behaviors are associated with psychopathology domains in a manner comparable to general obsessive-compulsive symptoms.



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“Association Splitting” Versus Cognitive Remediation in Obsessive-Compulsive Disorder: A Randomized Controlled Trial

Publication date: Available online 31 March 2018
Source:Journal of Anxiety Disorders
Author(s): Lena Jelinek, Marit Hauschildt, Birgit Hottenrott, Michael Kellner, Steffen Moritz
Studies have confirmed the efficacy of the cognitive intervention Association Splitting (AS) in obsessive-compulsive disorder (OCD) when applied as a self-help technique. AS aims to alter symptom-provoking automated cognitive networks of OC-related stimuli by building new or strengthening established but weak neutral associations. The aim of this study was to investigate the acceptance and benefits of therapist-assisted AS as an add-on to cognitive behavioral therapy (CBT). One hundred and nine patients with OCD who were undergoing CBT were randomly assigned to either AS or cognitive remediation (CR). Both groups were assessed at baseline, 4 weeks and 6 months later. The primary measure was the Yale-Brown Obsessive Compulsive Scale. Although patients' acceptance of AS was good, there was no evidence for the superiority of AS over CR regarding overall symptom severity. A larger decrease was found from baseline to 6 months follow-up in AS regarding avoidance. Moreover, subsidiary analyses excluding control patients who had obtained information about AS indicated its superiority. Despite high acceptance, we found no clear additional effect of AS beyond CBT treatment. Because superiority of AS was found in post hoc analyses excluding control patients who had obtained information on AS, we suggest that contagion effects deserve consideration.



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Max dD/Dt: A Novel Parameter to Assess Fetal Cardiac Contractility and a Substitute for Max dP/Dt

Publication date: Available online 2 April 2018
Source:Ultrasound in Medicine & Biology
Author(s): Yasuyuki Fujita, Ryo Kiyokoba, Yasuo Yumoto, Kiyoko Kato
Aortic pulse waveforms are composed of a forward wave from the heart and a reflection wave from the periphery. We focused on this forward wave and suggested a new parameter, the maximum slope of aortic pulse waveforms (max dD/dt), for fetal cardiac contractility. Max dD/dt was calculated from fetal aortic pulse waveforms recorded with an echo-tracking system. A normal range of max dD/dt was constructed in 105 healthy fetuses using linear regression analysis. Twenty-two fetuses with suspected fetal cardiac dysfunction were divided into normal and decreased max dD/dt groups, and their clinical parameters were compared. Max dD/dt of aortic pulse waveforms increased linearly with advancing gestational age (r = 0.93). The decreased max dD/dt was associated with abnormal cardiotocography findings and short- and long-term prognosis. In conclusion, max dD/dt calculated from the aortic pulse waveforms in fetuses can substitute for max dP/dt, an index of cardiac contractility in adults.



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