Search

Background and purpose: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) diagnosis are based on the presence of serological and magnetic resonance imaging (MRI) biomarkers. Diffusion tensor imaging (DTI), neurites orientation dispersion and density imaging (NODDI), and the Spherical Mean Technique (SMT) may be helpful to provide a microstructural characterization of the different types of white matter lesions and give an insight about their different pathological mechanisms. The aim of the study was to characterize microstructural differences between brain typical lesions (TLs) and nontypical lesions (nTLs). Methods: A total of 17 NMOSD and MOGAD patients [9 Aquaporin4 (AQP4) + NMO, 2 seronegative‐NMO, 6 MOGAD] underwent MRI scans on a 3 Tesla MAGNETON PRISMA. Diffusion parameters (fractional anisotropy; mean diffusivity [MD]; intracellular volume fraction [ICVF]; extra‐neurite transverse diffusivity; and extra‐neurite MD; neurite signal fraction) were obtained using DTI, NODDI, and SMT. Microstructural parameters within lesions were compared through a generalized linear model using age, sex, and total lesion volume as covariates. Results: In NMOSD/MOGAD whole cohort (total lesions = 477), TLs showed increased MD and decreased ICVF compared to nTLs (p <.05), indicating higher inflammation and axonal loss. Similar results were found also in the AQP4 + NMO subgroup (decreased ICVF, p <.05). Furthermore, in NMOSD/MOGAD whole cohort and in AQP4 + NMO subgroup, TLs showed a trend toward higher EXRATRANS than nTLs, suggesting a more severe degree of demyelination within TLs. Conclusions: TLs and nTLs in NMOSD/MOGAD showed different diffusion MRI‐derived microstructural features, with TLs showing a more severe degree of inflammation and fiber disruption with respect to nTLs. [ABSTRACT FROM AUTHOR]

Background: Monoaminergic systems are pharmacologically modulable and therefore both a target for symptomatic therapies and a window for the study of disease progression. Although these mechanisms are unclear. We explore the progression and the distribution of monoaminergic deficits in the Alzheimer's Disease (AD) continuum, along with the accumulation of misfolded pathological proteins. Method: We included 50 patients with Alzheimer's Disease (AD) and 42 Healthy Controls (HC). We acquired brain [18F]FDG‐PET images as a marker of neurodegeneration and MMSE as a measure of global cognitive functioning. We performed voxel‐based analysis between AD vs. HC. Using JuSpace toolbox we explored the correlation between [18F]FDG‐PET images and PET maps of dopamine (DAT), serotonin (SERT), noradrenaline (NAT) and choline vesicular (VAChT) transporters cortical distribution. Moreover, we evaluated relative hypometabolism in the main cholinergic nucleus (Meynert nucleus). We divided in two groups the AD patients based on MMSE score (AD Dementia ‐ADD‐ <24; MCI ≥24), to explore the association between monoaminergic disfunction and pathological proteins burden, across the AD continuum. Result: Sample characteristics are provided in Table 1. Results from voxel‐based analysis are shown in Figure 1. In the whole AD group, the distribution of relative cortical hypometabolism was associated with a significant reduction of VAChT availability (p = 0.018). This association remained significant when considering the ADD (p = 0.006), but not the MCI group. Figure 2. β‐amyloid42 levels and β‐amyloid42/40 ratio were inversely correlated with VAChT in the ADD group (p = 0.003; p = 0.038, respectively). No correlation was observed in the MCI group. Lastly, there was no correlation between Meynert nucleus relative hypometabolism and misfolded proteins levels in all groups. Conclusion: In the ADD phase we showed a significant damage in the cortical regions targeted by the cholinergic system. This result was not evident among the other systems studied, nor in the MCI phase. This provides an explanation of the reduction of the cholinesterase inhibitors efficiency in the dementia phase. Moreover, we showed that β‐amyloid accumulation was not associated with Meynert Nucleus degeneration, but that impacted on cholinergic function via damage accumulation in the cortical areas targeted by the cholinergic system. [ABSTRACT FROM AUTHOR]

Background: Intensive Care Units are emotionally intense environments where professional autonomy and interprofessional collaboration are essential. Nurses are at high risk of burnout, and the level of compassion satisfaction has a deep impact on the quality of their professional life. Although leadership styles and burnout have been the subject of an extensive body of research, there is an existing gap regarding the relationship between leadership strategies and intensive care nurses' quality of working life and the impact on their compassion satisfaction. Specifically, there is a lack of literature in southern European countries concerning the influence of organizational and cultural contexts. Aim: To evaluate the impact of nurse managers' leadership styles on Intensive Care Unit nurses' job satisfaction and compassion satisfaction. Design: A cross‐sectional study. Methods: An online set of validated tests was sent to a non‐probabilistic sample of nurses, recruited via the Italian association of intensive care and emergency nursing website. The set of tests consisted of the Empowering Leadership Questionnaire, Compassion Satisfaction Scale, and McCloskey Mueller Satisfaction Scale. Nurses actively working in intensive care and critical care settings were included in this study. ICU managers and leaders were excluded. Results: 308 nurses (response rate 63,2%) completed the questionnaires. Statistical analysis showed that the Leadership dimension of "Showing concern towards the team" had a significant effect on Compassion Satisfaction. In addition, this dimension had an effect on nurses' overall job satisfaction on five out of eight subscales. Conclusions: Leaders' authentic listening, communication, and participation capabilities have a positive impact on nurses' job and compassion satisfaction. The interest for team well‐being, taking time to discuss team concerns, and working closely with the team affects unpredicted factors like working hours, flexibility in shift scheduling, satisfaction about recognition, and career advancement. Relevance to clinical practice: Results suggest that nurse managers can draw on/adopt leadership strategies oriented to authentic listening and interaction with the team in order to manage organizational issues, increase nurses' professional quality of life and prevent burnout. [ABSTRACT FROM AUTHOR]

Which theoretical and empirical insights can inform language‐in‐education research that advances equitable and high‐quality learning at school? In this three‐part article, I first draw from various sources to foreground the urgent need to counteract linguicism and epistemic injustices and to commit to more just and rigorous scientific practices in research and education. Based on findings from my own research, I then argue that more just and rigorous practices need to attend to midadolescents’ individual differences in language learning. In response, I present insights from recent innovative evidence‐based pedagogical frameworks and tools that reveal promising paths forward. I close by calling for research with a dual focus on equity and rigor that supports moving away from “pedagogies of silence,” which silence marginalized students’ voices, damaging their identities and obstructing their learning, towards “pedagogies of voices,” which affirm all learners’ voices while amplifying their language repertoires and their critical learning. [ABSTRACT FROM AUTHOR]

Atypical connectivity between brain regions and altered structure of the corpus callosum (CC) in imaging studies supports the long‐distance hypoconnectivity hypothesis proposed for autism spectrum disorder (ASD). The aim of this study was to unveil the CC ultrastructural and cellular changes employing the valproic acid (VPA) rat model of ASD. Male Wistar rats were exposed to VPA (450 mg/kg i.p.) or saline (control) during gestation (embryonic day 10.5), and maturation, exploration, and social behavior were subsequently tested. Myelin content, ultrastructure, and oligodendroglial lineage were studied in the CC at post‐natal days 15 (infant) and 36 (juvenile). As a functional outcome, brain metabolic activity was determined by positron emission tomography. Concomitantly with behavioral deficits in juvenile VPA rats, the CC showed reduced myelin basic protein, conserved total number of axons, reduced percentage of myelinated axons, and aberrant and less compact arrangements of myelin sheath ultrastructure. Mature oligodendrocytes decreased and oligodendrocyte precursors increased in the absence of astrogliosis or microgliosis. In medial prefrontal and somatosensory cortices of juvenile VPA rats, myelin ultrastructure and oligodendroglial lineage were preserved. VPA animals exhibited global brain hypometabolism and local hypermetabolism in brain regions relevant for ASD. In turn, the CC of infant VPA rats showed reduced myelin content but preserved oligodendroglial lineage. Our findings indicate that CC hypomyelination is established during infancy and prior to oligodendroglial pattern alterations, which suggests that axon–oligodendroglia communication could be compromised in VPA animals. Thus, CC hypomyelination may underlie white matter alterations and contribute to atypical patterns of connectivity and metabolism found in ASD. [ABSTRACT FROM AUTHOR]

In this cluster randomized control trial study, the authors explored the efficacy of an intervention designed to improve second‐grade English learners' knowledge of challenging, high‐utility English vocabulary. The authors also examined whether the intervention had a differential effect on content words that differ on two attributes (cognate status and abstractness designation) and whether the effects lasted across time. Within schools, teachers were randomly assigned to treatment or control conditions, resulting in 12 treatment classrooms and 10 control classrooms. Teachers in the treatment condition developed vocabulary using six methods: interactive shared reading, direct instruction of individual words, instruction in cognate use, activities to foster word consciousness and reinforce instructed words, and use of visual and linguistic supports. Teachers in the control condition read the same books with the target vocabulary inserted into the stories. Findings on the curriculum‐based and standardized measure of vocabulary indicated that the intervention implemented for four 50‐minute lessons per week for 18 weeks was effective in helping English learners acquire challenging high‐utility school‐relevant vocabulary (Cohen's d = 1.88 for content words; d = 0.41 for connecting words; d = 0.47 for the Test of Oral Language Development). The effects differed by word characteristics, with higher effect sizes for words that are noncognates (d = 1.57 for both concrete and abstract noncognates; d = 1.02 concrete cognates; d = 0.81 for abstract cognates). Ten months after the intervention, treatment students still outperformed control students on content vocabulary learned during the intervention (d = 1.31). This study helps validate a multifaceted approach to vocabulary intervention and research. [ABSTRACT FROM AUTHOR]

The success of clinical trials of selective B‐cell depletion in patients with relapsing multiple sclerosis (MS) and primary progressive MS has led to a conceptual shift in the understanding of MS pathogenesis, away from the classical model in which T cells were the sole central actors and toward a more complex paradigm with B cells having an essential role in both the inflammatory and neurodegenerative components of the disease process. The role of B cells in MS was selected as the topic of the 27th Annual Meeting of the European Charcot Foundation. Results of the meeting are presented in this concise review, which recaps current concepts underlying the biology and therapeutic rationale behind B‐cell–directed therapeutics in MS, and proposes strategies to optimize the use of existing anti–B‐cell treatments and provide future directions for research in this area. ANN NEUROL 2021;89:13–23 [ABSTRACT FROM AUTHOR]

Background and purpose: The importance of upper limb function in multiple sclerosis (MS) is increasingly recognized, especially for the evaluation of patients with progressive MS with reduced mobility. Two sensor‐engineered gloves, able to measure quantitatively the timing of finger opposition movements, were previously used to assess upper limb disability in MS. The aims of the present study were: (1) to confirm the association between glove‐derived variables and standard measures of MS disability in a larger cohort; (2) to assess the correlation with quantitative magnetic resonance imaging (MRI) and quality of life (QoL) measures; and (3) to determine if the glove‐derived variables offer advantages over the standard measure for assessing upper limb function in MS, namely, the Nine‐Hole Peg Test (9HPT). Methods: Sixty‐five patients with MS, stable on disease‐modifying treatment, were evaluated at baseline using the glove, and through clinical examination (Expanded Disability Status Scale, Symbol Digit Modalities Test, Timed 25‐Foot Walk Test and 9HPT), MRI evaluation and QoL questionnaires. Correlations between the glove‐derived variables and clinical, MRI and QoL variables were assessed using Spearman's rank correlation coefficient analysis. Results: Glove‐derived variables significantly differed between patients with relapsing‐remitting and those with progressive MS, with similar or slightly higher correlations of the 9HPT with clinical variables. We found greater correlations of the QoL physical component with glove‐derived variables than with the 9HPT, and a significant correlation of its mental component with the glove‐derived variables but not with the 9HPT. Conclusion: The study results, confirming previous findings and showing advantages over the 9HPT, encourage the investigation of sensitivity to change in glove‐derived variables in a longitudinal setting. [ABSTRACT FROM AUTHOR]

Background and purpose: Limited data are available in the literature for upper limb impairment in multiple sclerosis (MS). This study aimed to report the distribution of values of hand grip strength (HGS), of the box and block test (BBT) and of the nine‐hole peg test (9HPT) correlated with demographic and clinical data in subjects with MS. Methods: This study involved five Italian neurological centres. The inclusion criteria were age ≥ 18, MS diagnosis, stable disease phase, right‐hand dominance. All subjects underwent HGS, BBT and 9‐HPT evaluation. Results: In all, 202 subjects with MS were enrolled: 137 females; mean age 48.4 years; mean Expanded Disability Status Scale (EDSS) 4.17; mean disease duration 14.12 years; disease course 129 relapsing–remitting, 21 primary progressive and 52 secondary progressive MS subjects; mean right HGS 25.3 kg, left 23.2 kg; mean right BBT 45.7 blocks, left 44.9 blocks; mean right 9‐HPT 30.7 s, left 33.4 s. All results were statistically significantly different compared to healthy controls. HGS, BBT and 9‐HPT were associated with age, EDSS and disease duration, whilst disease course correlated with BBT and 9‐HPT. The BBT and 9‐HPT scores significantly differed according to level of disability (EDSS ≤3.0, 3.5–5.5, ≥6.0). Conclusion: Hand grip strength and BBT value distribution in a large MS population is reported. Correlations between HGS, BBT and 9‐HPT were generally low. [ABSTRACT FROM AUTHOR]

Academic language skills support mid‐adolescents' comprehension of the language of school texts. To date, scarce research has explored associations between dual academic language skills and reading comprehension among mid‐adolescent dual language immersion (DLI) students. This study examined individual differences in Spanish and English academic language skills and their contribution to English reading comprehension in a cross‐sectional sample of DLI students in Grades 4–6 (N = 101). Taking advantage of a recently proposed construct, the core academic language skills (CALS), and the CALS instruments available in Spanish and English, dual academic language skills were examined as predictors of English reading comprehension. Results revealed that Spanish and English CALS were both significant predictors of English reading comprehension even after accounting for students' sociodemographic background, English proficiency designation, and English word reading fluency. Findings underscore the cross‐linguistic contribution of Spanish academic language skills to English reading comprehension and highlight the importance of promoting these skills in both languages to support mid‐adolescent DLI students' biliteracy development. [ABSTRACT FROM AUTHOR]

Background and purpose: The literature provides contrasting results on the efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients with cerebellar signs. It was sought to evaluate the efficacy of LEV on upper limb movement in MS patients. Methods: In this multicenter double‐blind placebo‐controlled crossover study, MS patients with prevalently cerebellar signs were randomly allocated into two groups: LEV followed by placebo (group 1) or placebo followed by LEV (group 2). Clinical assessments were performed by a blinded physician at T0 (day 1), T1 (day 22), T2 (2‐week wash‐out period, day 35) and T3 (day 56). The primary outcome was dexterity in the arm with greater deficit, assessed by the nine‐hole peg test (9HPT). Secondary clinical outcomes included responders on the 9HPT (∆9HPT >20%), tremor activity of the daily living questionnaire and self‐defined upper limb impairment, through a numeric rating scale. Kinematic evaluation was performed using a digitizing tablet, providing data on normalized jerk, aiming error and centripetal acceleration. Results: Forty‐eight subjects (45.2 ± 10.4 years) were randomly allocated into two groups (n = 24 each). 9HPT significantly improved in the LEV phase in both groups (P < 0.001). The LEV treatment phase led to a significant improvement (P < 0.01) of all clinical outcomes in group 1 and in dexterity in group 2. No significant changes were reported during both placebo phases in the two groups. Considering the kinematic analysis, only normalized jerk significantly improved after treatment with LEV (T0–T1) in group 1. Conclusions: Levetiracetam treatment seems to be effective in improving upper limb dexterity in MS patients with cerebellar signs. [ABSTRACT FROM AUTHOR]

Background: The inability to comply with enhanced recovery protocols (ERp) after pancreaticoduodenectomy (PD) is a real but understated issue. Our goal is to report our experience and a potential tool to predict ERp failure in order to better characterize this problem. Methods: From January 1, 2014, to January 31, 2016, 205 consecutive patients underwent PD in our center and were managed according to an ERp. Failure to comply with postoperative protocol items was defined as any of: no active ambulation on postoperative day 1 (POD1); less than 4 h out of bed on POD2; removal of nasogastric tube and bladder catheter after POD1 and POD3, respectively; reintroduction of oral feeding after POD4; and continuation of intravenous infusions after POD4. Data were collected in a prospective database. Results: Taking in consideration the number of failed items and the length of stay, we defined failure of the ERp as no compliance to two or more items. A total of 116 patients (56.6%) met this definition of failure. We created a predictive model consisting of age, BMI, operative time, and pancreatic stump consistency. These variables were independent predictors of failure (OR 1.03 [1.001–1.06] p = 0.01; OR 1.11 [1.01–1.22] p = 0.03; OR 1.004 [1.001–1.009] p = 0.02 and OR 2.89 [1.48–5.67] p = 0.002, respectively). Patient final score predicted the failure of the ERp with an area under the ROC curve of 0.747. Conclusions: It seems to be possible to predict ERp failure after PD. Patients at high risk of failure may benefit more from a specific ERp. [ABSTRACT FROM AUTHOR]

Background and purpose: The best therapeutic approach for aggressive relapsing–remitting multiple sclerosis remains unknown. The objective was to compare the efficacy and safety of autologous haematopoietic stem cell transplantation (aHSCT) and alemtuzumab in aggressive relapsing–remitting multiple sclerosis. Methods: The time to first relapse, time to confirmed disability worsening, time to first evidence of magnetic resonance imaging (MRI) activity and time to first evidence of disease activity were compared between the two treatment groups. Secondary outcomes included the 12, 24 and 36 month annualized relapse rate (ARR) and the 6‐month confirmed Expanded Disability Status Scale (EDSS) changes at months 12 and 24. Results: Fifty‐seven patients treated with aHSCT (n = 25) or alemtuzumab (n = 32) were included. At baseline, aHSCT patients had a higher EDSS (median score 6 vs. 3; P < 0.001), higher ARR (mean ARR 3.2 vs. 1.7; P = 0.001) and a higher number of baseline T1 gadolinium‐enhancing lesions on MRI (mean number 15.5 vs. 1.6; P < 0.001). NEDA‐3 (no evidence of disease activity) status was more frequently achieved in aHSCT‐treated patients than in alemtuzumab‐treated patients [75% vs. 56% of patients at the end of the observation period; hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.08–0.84; P = 0.023]. aHSCT significantly reduced the risk of relapse (relapse‐free survival 84% vs. 69%; HR 0.13, 95% CI 0.02–0.63; P = 0.012) and MRI activity (MRI‐activity‐free survival 85% vs. 59%; HR 0.13, 95% CI 0.03–0.59; P = 0.009). The ARR at 36 months was significantly lower in the aHSCT group (0.05 vs. 0.35, P = 0.02). A significant effect of aHSCT in promoting EDSS improvement compared with alemtuzumab was noted (P = 0.035). Conclusions: Alemtuzumab and aHSCT are effective treatment choices for aggressive multiple sclerosis. aHSCT seems to be superior to alemtuzumab in inducing complete disease control and in promoting short‐term disability improvement. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of cholecalciferol (vitamin D3) supplementation on peripheral immune cell frequency and N‐glycan branching in patients with relapsing‐remitting multiple sclerosis (RRMS). Methods: Exploratory analysis of high‐dose (20 400 IU) and low‐dose (400 IU) vitamin D3 supplementation taken every other day of an 18‐month randomized controlled clinical trial including 38 RRMS patients on stable immunomodulatory therapy (NCT01440062). We investigated cholecalciferol treatment effects on N‐glycan branching using L‐PHA stain (phaseolus vulgaris leukoagglutinin) at 6 months and frequencies of T‐, B‐, and NK‐cell subpopulations at 12 months with flow cytometry. Results: High‐dose supplementation did not change CD3+ T cell subsets, CD19+ B cells subsets, and NK cells frequencies, except for CD8+ T regulatory cells, which were reduced in the low‐dose arm compared to the high‐dose arm at 12 months. High‐dose supplementation decreased N‐glycan branching on T and NK cells, measured as L‐PHA mean fluorescence intensity (MFI). A reduction of N‐glycan branching in B cells was not significant. In contrast, low‐dose supplementation did not affect N‐glycan branching. Changes in N‐glycan branching did not correlate with cell frequencies. Interpretation: Immunomodulatory effect of vitamin D may involve regulation of N‐glycan branching in vivo. Vitamin D3 supplementation did at large not affect the frequencies of peripheral immune cells. [ABSTRACT FROM AUTHOR]

Merging evidence from psychological models of reading comprehension, ethnographic research on language and literacy, and textual linguistics lines of research, the authors take the position that psychological models of reading comprehension often overlook written language comprehension and production as context‐embedded, sociocultural processes. Using the example of academic language comprehension by middle grade learners, the authors present a series of studies that have informed the science of reading by making visible a precise set of high‐utility academic language skills that support informational text comprehension during middle childhood (ages 9–14). Studies have suggested that these skills develop gradually throughout adolescence and significantly contribute to reading comprehension. Drawing on this research with the goal of informing the science of reading, the authors suggest that academic language comprehension involves for the reader (a) familiarity with a set of academic language forms commonly found in school texts, (b) experience with the sociocultural practices of understanding and using the academic language of text within a particular sociocultural community, and (c) aligning with or resisting the reader identities implied by the language of a text. The authors suggest that innovative research and pedagogical approaches are needed to broaden the conceptualization of language and reading comprehension relations from purely cognitive into one that embraces the reader's interaction with a text as a sociocultural phenomenon. [ABSTRACT FROM AUTHOR]

This study reports on the conceptualization of a new construct targeting the cross‐disciplinary academic language skills most relevant to school reading comprehension, targeting the validation of the Core Academic Language Skills (CALS) Instrument, a novel assessment tool which measures this construct. Participants included Grade 4–8 monolingual English and bilingual students designated as English learners (N = 7,152) from the United States. The study investigated the dimensionality of the core academic language skills construct, the reliability and validity of the CALS Instrument, and the impact of school grade on students' performance in core academic language skills. Results revealed the assessment measure to be unidimensional and to discriminate performance by grade level. This study offers insight into the value of measuring cross‐disciplinary school‐relevant language proficiency, delineates skills to be targeted through instruction to support reading comprehension, and offers a tool to identify students who will benefit most from this instruction. [ABSTRACT FROM AUTHOR]

This study examines whether children's decontextualized talk-talk about nonpresent events, explanations, or pretend-at 30 months predicts seventh-grade academic language proficiency (age 12). Academic language (AL) refers to the language of school texts. AL proficiency has been identified as an important predictor of adolescent text comprehension. Yet research on precursors to AL proficiency is scarce. Child decontextualized talk is known to be a predictor of early discourse development, but its relation to later language outcomes remains unclear. Forty-two children and their caregivers participated in this study. The proportion of child talk that was decontextualized emerged as a significant predictor of seventh-grade AL proficiency, even after controlling for socioeconomic status, parent decontextualized talk, child total words, child vocabulary, and child syntactic comprehension. [ABSTRACT FROM AUTHOR]

Abstract: Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, whose best‐understood mechanism is sprouting. However, therapeutic VEGF delivery to ischemic muscle induces angiogenesis by the alternative process of intussusception, or vascular splitting, whose molecular regulation is essentially unknown. Here, we identify ephrinB2/EphB4 signaling as a key regulator of intussusceptive angiogenesis and its outcome under therapeutically relevant conditions. EphB4 signaling fine‐tunes the degree of endothelial proliferation induced by specific VEGF doses during the initial stage of circumferential enlargement of vessels, thereby limiting their size and subsequently enabling successful splitting into normal capillary networks. Mechanistically, EphB4 neither inhibits VEGF‐R2 activation by VEGF nor its internalization, but it modulates VEGF‐R2 downstream signaling through phospho‐ERK1/2. In vivo inhibitor experiments show that ERK1/2 activity is required for EphB4 regulation of VEGF‐induced intussusceptive angiogenesis. Lastly, after clinically relevant VEGF gene delivery with adenoviral vectors, pharmacological stimulation of EphB4 normalizes dysfunctional vascular growth in both normoxic and ischemic muscle. These results identify EphB4 as a druggable target to modulate the outcome of VEGF gene delivery and support further investigation of its therapeutic potential. [ABSTRACT FROM AUTHOR]

Abstract: Although literacy achievement has improved in Chile, adolescents’ underperformance in reading comprehension is still a serious concern. In English, core academic‐language skills (CALS) have been found to significantly predict reading comprehension, even controlling for academic vocabulary knowledge. CALS are high‐utility language skills that support reading comprehension across school content areas. Guided by an operational definition of Spanish CALS (S‐CALS), three goals drove this study: to develop two psychometrically reliable tests, the S‐CALS Instrument and the Spanish Academic Vocabulary (S‐AVoc) Test; to explore the dimensionality of core academic‐language proficiencies, as measured by these two tests; and to examine the contribution of core academic‐language proficiencies to reading comprehension. A cross‐sectional sample of 810 Chilean students (grades 4–8) participated in four assessments that measured standardized reading comprehension, word‐reading fluency, Spanish academic vocabulary, and S‐CALS. Using classical test theory and item response theory analyses, results yielded robust reliability evidence for both instruments. Consistent with prior research, S‐CALS and academic vocabulary scores displayed upward trends in higher grades yet considerable within‐grade variability. Confirmatory factor analysis revealed that S‐CALS and S‐AVoc were best conceptualized as part of a higher order construct, the Spanish core academic‐language and vocabulary skills (S‐CALVS). The aggregated S‐CALVS scores predicted reading comprehension, beyond the contribution of grade, school factors, and word‐reading fluency. This study advances our scientific understanding of CALS as relevant for adolescent literacy beyond the English language. The high‐utility school‐relevant language and vocabulary skills offer promising tools to inform and evaluate innovative reading comprehension interventions for Spanish‐speaking adolescents. [ABSTRACT FROM AUTHOR]

Educators are aware of the need to promote students' academic language to support text comprehension. Yet, besides teaching academic vocabulary, many educators continue to ask, What would this instruction entail? Guided by a new framework known as core academic language skills ( CALS), the authors' research focuses on delineating core language skills that contribute to reading comprehension to make them more visible to educators and researchers. In this article, findings from two studies are integrated to argue for a mixed-methods approach to advance academic language research and pedagogy. In study 1, the authors assessed upper elementary/middle school students' CALS and quantitatively examined the association between CALS and reading comprehension. In study 2, the authors used qualitative methods to collect and analyze students' oral reflections about academic language. Key findings from these studies and their implications for academic language pedagogy in today's schools are discussed. [ABSTRACT FROM AUTHOR]

This study examines whether children’s decontextualized talk—talk about nonpresent events, explanations, orpretend—at 30 months predicts seventh-grade academic language proficiency (age 12). Academic language(AL) refers to the language of school texts. AL profi ciency has been identified as an important predictor ofadolescent text comprehension. Yet research on precursors to AL proficiency is scarce. Child decontextualizedtalk is known to be a predictor of early discourse development, but its relation to later language outcomesremains unclear. Forty-two children and their caregivers participated in this study. The proportion of childtalk that was decontextualized emerged as a significant predictor of seventh-grade AL proficiency, even aftercontrolling for socioeconomic status, parent decontextualized talk, child total words, child vocabulary, andchild syntactic comprehension.

Persistent organic pollutants (POPs), such as PCBs (polychlorinated biphenyls) and DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], are environmental contaminants with potential endocrine disrupting activity. DNA methylation levels in peripheral blood lymphocytes have been associated with serum concentrations of POPs in Greenland Inuit and Korean populations. Greenland Inuits are characterized by the highest worldwide POP levels. In this cross-sectional study we evaluated the relationship between serum POP concentrations and DNA methylation levels in sperm of non-occupationally exposed fertile men from Greenland, Warsaw (Poland), and Kharkiv (Ukraine). Serum levels of PCB-153 [1,2,4-trichloro-5-(2,4,5-trichlorophenyl)benzene], as a proxy of the total PCBs body burden, and of p, p'-DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene], the main metabolite of DDT were measured. Sperm DNA methylation level was assessed globally by flow cytometric (FCM) immunodetection of 5-methyl-cytosines and at specific repetitive DNA sequences (Alu, LINE-1, Satα) by PCR-pyrosequencing after bisulfite conversion. Multivariate linear regression analysis was applied to investigate correlations between serum POP concentrations and DNA methylation. No consistent associations between exposure to POPs and sperm DNA methylation at repetitive DNA sequences were detected. A statistically significant global decrease in methylation was associated with exposure to either POP by FCM analysis. This is the first study to investigate environmental exposure to POPs and DNA methylation levels considering sperm as the target cells. Although POP exposure appears to have a limited negative impact on sperm DNA methylation levels in adult males, the global hypomethylation detected by one of the methods applied suggests that further investigation is warranted. Environ. Mol. Mutagen. 57:200-209, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are being increasingly investigated as a therapeutic alternative, not only for their possible regenerative potential but also for their immunomodulatory action, which is being exploited for controlling diseases associated with inflammation. Understanding their direct and indirect target cells, as well as their mode of action and relevant pathways, is a prerequisite for the appropriate and optimal use of MSCs in therapy. Here, we review recent findings on the effects of MSCs on adaptive and innate immune cells. We also consider the impact of the environment on MSC profile, both anti- and proinflammatory, and the mechanisms and molecular pathways through which their effects are mediated, both at theMSC and target cell levels. [ABSTRACT FROM AUTHOR]

Despite a long-standing awareness of academic language as a pedagogically relevant research area, the construct of academic-language proficiency, understood as a more comprehensive set of skills than just academic vocabulary, has remained vaguely specified. In this study, we explore a more inclusive operationalization of an academic-language proficiency construct, core academic-language skills ( CALS). CALS refers to a constellation of high-utility language skills hypothesized to support reading comprehension across school content areas. Using the Core Academic Language Skills Instrument ( CALS-I), a theoretically grounded and psychometrically robust innovative tool, we first examined the variability in students' CALS by grade, English-proficiency designation, and socioeconomic status ( SES). Then, we examined the contribution of CALS to reading comprehension using academic vocabulary knowledge, word reading fluency, and sociodemographic factors as covariates. A linguistically and socioeconomically diverse cross-sectional sample of 218 students (grades 4-6) participated in four assessments: the CALS-I, a standardized reading comprehension assessment (Gates-MacGinitie Reading Test), an academic vocabulary test (Vocabulary Association Test), and a word reading fluency test (Test of Silent Word Reading Fluency). General linear model analysis of variance revealed that CALS differed significantly by grade, English-proficiency designation, and SES, with students in higher grades, English-proficient students, and those from higher SES backgrounds displaying higher scores, on average. Hierarchical multiple regression analyses identified CALS as an independent predictor of reading comprehension, even after controlling for academic vocabulary knowledge, word reading fluency, and sociodemographic factors. By specifying a set of language skills associated with reading comprehension, this study advances our understanding of school-relevant language skills, making them more visible for researchers and educators. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl substances (PFASs) are widely used in a variety of industrial processes and products, and have been detected globally in humans and wildlife. PFASs are suspected to interfere with endocrine signaling and to adversely affect human reproductive health. The aim of the present study was to investigate the associations between exposure to PFASs and sperm global methylation levels in a population of non-occupationally exposed fertile men. Measurements of PFASs in serum from 262 partners of pregnant women from Greenland, Poland and Ukraine, were also carried out by liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) were detected in 97% of the blood samples. Two surrogate markers were used to assess DNA global methylation levels in semen samples from the same men: (a) average DNA methylation level in repetitive DNA sequences (Alu, LINE-1, Satα) quantified by PCR-pyrosequencing after bisulfite conversion; (b) flow cytometric immunodetection of 5-methyl-cytosines. After multivariate linear regression analysis, no major consistent associations between PFASs exposure and sperm DNA global methylation endpoints could be detected. However, since weak but statistically significant associations of different PFASs with DNA hypo- and hyper-methylation were found in some of the studied populations, effects of PFASs on sperm epigenetic processes cannot be completely excluded, and this issue warrants further investigation. Environ. Mol. Mutagen. 55:591-600, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background and Purpose Altered glutamate exocytosis and c AMP production in cortical terminals of experimental autoimmune encephalomyelitis ( EAE) mice occur at the early stage of disease (13 days post-immunization, d.p.i.). Neuronal defects were paralleled by overexpression of the central chemokine CCL5 (also known as RANTES), suggesting it has a role in presynaptic impairments. We propose that drugs able to restore CCL5 content to physiological levels could also restore presynaptic defects. Because of its efficacy in controlling CCL5 overexpression, desipramine ( DMI) appeared to be a suitable candidate to test our hypothesis. Experimental Approach Control and EAE mice at 13 d.p.i. were acutely or chronically administered DMI and monitored for behaviour and clinical scores. Noradrenaline and glutamate release, c AMP, CCL5 and TNF-α production were quantified in cortical synaptosomes and homogenates. Peripheral cytokine production was also determined. Key Results Noradrenaline exocytosis and α2-adrenoeceptor-mediated activity were unmodified in EAE mice at 13 d.p.i. when compared with control. Acute, but not chronic, DMI reduced CCL5 levels in cortical homogenates of EAE mice at 13 d.p.i., but did not affect peripheral IL-17 and TNF-α contents or CCL5 plasma levels. Acute DMI caused a long-lasting restoration of glutamate exocytosis, restored endogenous c AMP production and impeded the shift from inhibition to facilitation of the CCL5-mediated control of glutamate exocytosis. Finally, DMI ameliorated anxiety-related behaviour but not motor activity or severity of clinical signs. Conclusions We propose DMI as an add-on therapy to normalize neuropsychiatric symptoms in multiple sclerosis patients at the early stage of the disease. [ABSTRACT FROM AUTHOR]

Microglia cells, the resident innate immune cells in the brain, are highly active, extending and retracting highly motile processes through which they continuously survey their microenvironment for 'danger signals' and interact dynamically with surrounding cells. Upon sensing changes in their central nervous system microenvironment, microglia become activated, undergoing morphological and functional changes. Microglia activation is not an 'all-or-none' process, but rather a continuum depending on encountered stimuli, which is expressed through a spectrum of molecular and functional phenotypes ranging from so-called 'classically activated', with a highly pro-inflammatory profile, to 'alternatively activated' associated with a beneficial, less inflammatory, neuroprotective profile. Microglia activation has been demonstrated in most neurological diseases of diverse aetiology and has been implicated as a contributor to neurodegeneration. The possibility to promote microglia's neuroprotective phenotype has therefore become a therapeutic goal. We have focused our discussion on the role of microglia in multiple sclerosis, a prototype of inflammatory, demyelinating, neurodegenerative disease, and on the effect of currently approved or on-trial anti-inflammatory therapeutic strategies that might mediate neuroprotection at least in part through their effect on microglia by modifying their behaviour via a switch of their functional phenotype from a detrimental to a protective one. In addition to pharmaceutical approaches, such as treatment with glatiramer acetate, interferonb, fingolimod or dimethyl fumarate, we address the alternative therapeutic approach of treatment with mesenchymal stem cells and their potential role in neuroprotection through their 'calming' effect on microglia. [ABSTRACT FROM AUTHOR]

To perform their distinct effector functions, pathogen-specific T cells have to migrate to target tissue where they recognize antigens and produce cytokines that elicit appropriate types of protective responses. Similarly, migration of pathogenic self-reactive T cells to target organs is an essential step required for tissue-specific autoimmunity. In this article, we review data from our laboratory as well as other laboratories that have established that effector function and migratory capacity are coordinately regulated in different T-cell subsets. We then describe how pathogenic T cells can enter into intact or inflamed central nervous system (CNS) to cause experimental autoimmune encephalomyelitis or multiple sclerosis. In particular, we elaborate on the role of CCR6/CCL20 axis in migration through the choroid plexus and the involvement of this pathway in immune surveillance of and autoimmunity in the CNS. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study that determines if anti-thyroid antibodies are found in the follicular milieu of women who are euthyroid infertile and with thyroid autoimmunity and undergoing in vitro fertilization (IVF). It also examines the IVF outcome in affected women in terms of negative controls. The method of the study is described, including measurement of the anti-thyroglobulin and anti-thyroperoxidase levels. The study concludes that anti-thyroid antibodies in ovarian follicles plays a role in female infertility.

J. Neurochem. (2010) 115, 343-352. Abstract We have investigated the spontaneous and the depolarisation-induced release of [3H] d-aspartate ([3H] d-ASP), a non-metabolisable analogue of glutamate, in spinal cord slices, synaptosomes and gliosomes from mice with experimental autoimmune encephalomyelitis (EAE) at 13, 21 and 55 days post-immunisation (d.p.i.), representing onset, peak and chronic phases of the pathology. At 13 and 21 d.p.i., the KCl-evoked, calcium-dependent overflow of [3H] d-ASP in spinal cord slices was significantly lower (30-40%), whereas at 55 d.p.i. it was significantly higher (30%), than that elicited in matched controls. When the release was measured from spinal cord synaptosomes and gliosomes in superfusion, a different picture emerged. The spontaneous and the KCl(15 mM)-induced release of [3H] d-ASP were significantly increased both in synaptosomes (17% and 45%, respectively) and gliosomes (26% and 25%, respectively) at 21, but not at 13, d.p.i. At 55 d.p.i., the KCl-induced [3H] d-ASP release was significantly increased (40%) only in synaptosomes. Finally, uptake of [3H] d-ASP was markedly (50-60%) increased in spinal cord synaptosomes, but not in gliosomes, obtained from EAE mice at 21 d.p.i., whereas no differences could be detected at 13 d.p.i. Our data indicate that glutamatergic neurotransmission is altered in the spinal cord of EAE mice. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered a promising tool for the treatment of immune-mediated diseases. This study was undertaken to assess the influence of murine BM-MSCs on the activation of B cells in (NZB x NZW)F(1) mice as an animal model of systemic lupus erythematosus (SLE). METHODS: We evaluated the in vitro effects of BM-MSCs on the proliferation and differentiation to plasma cells of splenic mature B cell subsets, namely follicular and marginal zone B cells isolated from (NZB x NZW)F(1) mice. Lupus mice were also treated with BM-MSCs, and serum autoantibodies, proteinuria, histologic changes in the kidney, and survival rates were monitored. RESULTS: BM-MSCs inhibited antigen-dependent proliferation and differentiation to plasma cells of follicular and marginal zone B cells in vitro. This inhibitory effect was dependent on interferon-[gamma] (IFN[gamma]) and was mediated by cell-to-cell contact, involving the programmed death 1 (PD-1)/PD ligand pathway. In vivo treatment with BM-MSCs did not affect the levels of anti-double-stranded DNA antibodies or proteinuria. However, a reduction in glomerular immune complex deposition, lymphocytic infiltration, and glomerular proliferation was observed. CONCLUSION: Our findings indicate that BM-MSCs affect B cell receptor-dependent activation of both follicular and marginal zone B cells from lupus mice. This inhibitory effect is IFN[gamma]-dependent and cell contact-dependent. MSCs in vivo do not affect the production of autoantibodies, the level of proteinuria, or the mortality rates. Nonetheless, the significant improvement in histologic findings in the kidney supports the potential role of MSCs in the prevention of glomerular damage. [ABSTRACT FROM AUTHOR]

The article explores the interferon-γ-dependent inhibition of B cell activation through bone marrow-derived mesenchymal stem cells (BM-MSCs) in a murin model of systemic lupus erythematosus (SLE). The in vitro effects of BM-MSCs on the proliferation and differentiation to plasma cells of splenic mature B cell subsets were evaluated in lupus mice. It was found out that BM-MSCs affect B cell receptor-dependent activation of both follicular and marginal zone B cells. It added that MSCs in vivo has no effect on the production of autoantibodies.

Experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis, is characterized by demyelination, inflammation and neurodegeneration of CNS in which free radicals play a role. Recently, the efficacy of murine mesenchimal stem cells (MSCs) as treatment of EAE induced in mice by the encephalitogenic peptide MOG(35–55) was demonstrated. The present study analyzed some markers of oxidative stress, inflammation/degeneration and apoptosis such as metallothioneins (MTs), antioxidant enzymes (superoxide dismutase, catalase and glutathione- S-transferase), poly(ADP-ribose) polymerase-1 and p53 during EAE progression and following MSC treatment. Expression of the three brain MT isoforms increased significantly in EAE mice compared with healthy controls, but while expression of MT-1 and MT-3 increased along EAE course, MT-2 was up-regulated at the onset, but returned to levels similar to those of controls in chronic phase. The changes in the transcription and activity of the antioxidant enzymes and in expression of poly(ADP-ribose) polymerase-1 and p53 showed the same kinetics observed for MT-1 and MT-3 during EAE. Interestingly, i.v. administration of MSCs reduced the EAE-induced increases in levels/activities of all these proteins. These results support an antioxidant and neuroprotective activity for MSCs that was also confirmed in vitro on neuroblastoma cells exposed to an oxidative insult. [ABSTRACT FROM AUTHOR]

This paper deals with hydrologic studies relevant to the works engineered for the protection of the city of Venice (Italy) from major flooding under significant climate change scenarios. Such works foresee the temporary closure of the lagoon surrounding the city to tidal exchanges with the Adriatic Sea in times of sea storm surges via the operation of a set of mobile gates. A general hydrologic model of the ∼2000 km2 mainland contributing runoff to the lagoon of Venice is coupled in time and space with a 2-D finite element model of the relevant tidal hydrodynamics to forecast maximum lagoonal surges in times of closure. We also study the impacts of run-through discharges bypassing the mobile gates and wind setups at time scales comparable to the foreseen closures (from a few to tens of hours). Climate change scenarios are recapitulated by up to +50 cm relative sea level rises by 2100 (the projected lifetime of the current protection works). Possible flooding of the city due to residual fluxes entering the lagoon during prolonged closures is examined. A probabilistic framework is also proposed for computing the statistics of maximum lagoon rises and stage-rise durations. Our studies suggest the adequacy of the design of temporary closures with respect to flooding and provide methods for general exercises in assessing the impact of regional climate change scenarios. [ABSTRACT FROM AUTHOR]

The first autologous hematopoietic stem cell transplantation in Europe for a patient with severe refractory systemic lupus erythematosus (SLE) was performed in Genoa in 1996. Since then, 32 patients with a wide spectrum of autoimmune diseases (ADs) received autologous transplants, 22 of them with multiple sclerosis (MS). There were no fatal adverse events. All patients had complete or very good partial remissions, but relapses were frequent, especially in SLE, though never as aggressive as pretransplant. The mechanism of action of this intervention remains not completely understood, as briefly discussed here. [ABSTRACT FROM AUTHOR]

To evaluate the ability of mesenchymal stem cells (MSCs), a subset of adult stem cells from bone marrow, to cure experimental autoimmune encephalomyelitis.The outcome of the injection of MSCs, in mice immunized with the peptide 139–151 of the proteolipid protein (PLP), was studied analyzing clinical and histological scores of treated mice. The fate of MSCs labeled with the green fluorescent protein was tracked in vivo by a photon emission imaging system and postmortem by immunofluorescence. The modulation of the immune response against PLP was studied through the analysis of in vivo T‐ and B‐cell responses and by the adoptive transfer of MSC‐treated encephalitogenic cells.MSC‐treated mice showed a significantly milder disease and fewer relapses compared with control mice, with decreased number of inflammatory infiltrates, reduced demyelination, and axonal loss. In contrast, no evidence of green fluorescent protein–labeled neural cells was detected inside the brain parenchyma, thus not supporting the hypothesis of MSCs transdifferentiation. In vivo, PLP‐specific T‐cell response and antibody titers were significantly lower in MSC‐treated mice. When adoptively transferred, encephalitogenic T cells activated against PLP139–151 in the presence of MSCs induced a milder disease compared with that induced by untreated encephalitogenic T cells. These cells showed decreased production of interferon‐γ and tumor necrosis factor‐α and did not proliferate on antigen recall, and thus were considered anergic.Overall, these findings suggest that the beneficial effect of MSCs in experimental autoimmune encephalomyelitis is mainly the result of an interference with the pathogenic autoimmune response. Ann Neurol 2007;61:219–227 [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non-mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA-incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno-mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell-to-cell interactions, but also by environmental factors shaping their phenotype and functions. [ABSTRACT FROM AUTHOR]

Could arterial spin labelling perfusion imaging uncover the invisible in N-methyl-d-aspartate receptor encephalitis? Few reports exist on the utility of magnetic resonance imaging (MRI) perfusion techniques in NMDAR encephalitis. Arterial spin labeling perfusion imaging demonstrates cerebral hyperperfusion in anti-NMDAR encephalitis. [Extracted from the article]

Although graft vs. host disease (GvHD) is a frequent complication of allogeneic bone marrow transplantation (BMT), involvement of the central and peripheral nervous systems (CNS and PNS, respectively) has not been demonstrated conclusively. Here, we report of a patient who, following allogeneic BMT for lymphoblastic T-cell lymphoma, suffered a syndrome characterized by self-remitting cerebellar and pyramidal signs associated with a progressive involvement of the peripheral nervous system (PNS). Clinical course and laboratory findings correlated with relapses of systemic GvDH, thus suggesting the possibility that involvement of CNS and PNS may be sustained by a similar pathogenic mechanism. [ABSTRACT FROM AUTHOR]

The paper describes the process of building Internet-transmittable, 3-D digital virtual models of ancient heritage monuments from on-site data, focusing especially on 3-D dimensional data acquisition techniques and color processing methods. Section 1 considers project goals and the attendant problems; Section 2 provides a brief summary of state-of-the-art experience and the technologies adopted by the Authors; Section 3 illustrates the key features of the 3-D color data acquisition methods used as well as the shape and color processing pipeline; Section 4 describes the specific study conducted on single elements and faades of the Coliseum in Rome, while Section 6 outlines future work. [ABSTRACT FROM AUTHOR]