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1.
J Sch Health ; 94(7): 638-646, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38263947

RESUMEN

BACKGROUND: Return to school supports are recommended to facilitate adolescents' re-entry to school following a concussion. However, little is known as to what school stakeholders prefer for a return-to-school process. This study sought to describe the preferences of high school students, parents, and educators for a Return-to-School Framework for adolescents following a concussion. METHODS: We conducted qualitative semi-structured, 1-on-1 or group interviews with high school students (n = 6), parents (n = 5), and educators (n = 15) from Calgary, Canada. Interviews aimed to describe participants' preferences for a Return-to-School Framework for students following a concussion. Interviews were analyzed using conventional content analysis. RESULTS: We organized the data into 4 main themes: (1) purpose of the Return-to-School Framework; (2) format and operation of the Return-to-School Framework; (3) communication about a student's concussion; and (4) necessity of concussion education for students and educators. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: A Return-to-School Framework following concussion should be developed in consultation with families, educators, and students and supports should be tailored to each student. CONCLUSIONS: Participants preferred a standardized and consistent Return-to-School Framework including ongoing communication between stakeholders as well as feasible and individualized school supports.


Asunto(s)
Conmoción Encefálica , Regreso a la Escuela , Estudiantes , Humanos , Adolescente , Masculino , Femenino , Estudiantes/psicología , Investigación Cualitativa , Padres/psicología , Entrevistas como Asunto , Instituciones Académicas , Canadá , Servicios de Salud Escolar , Alberta , Participación de los Interesados
2.
Pediatr Crit Care Med ; 25(4): e193-e204, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38059739

RESUMEN

OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.


Asunto(s)
Analgesia , Enfermedad Crítica , Lactante , Niño , Humanos , Enfermedad Crítica/terapia , Reproducibilidad de los Resultados , Analgesia/métodos , Dolor , Respiración Artificial , Hipnóticos y Sedantes/uso terapéutico
3.
Pediatr Blood Cancer ; 71(3): e30807, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38110802

RESUMEN

BACKGROUND: Children with sickle cell disease (SCD) are at risk for physical, psychological, and social adjustment challenges. This study sought to investigate social adjustment and related factors in children living with SCD. METHODS: Data from 32 children (50% male, mean age = 10.32 years, SD = 3.27) were retrospectively collected from a neuropsychology clinic at a tertiary care pediatric hospital. Social adjustment was measured using the Behavior Assessment System for Children (BASC-3) parent-proxy, withdrawal subscale, and the Pediatric Quality of Life Inventory (PedsQL) Generic Module Social Functioning self- and parent-proxy subscales. Other measures captured executive functioning (i.e., Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) Parent Form) and non-disease-related associations with social adjustment, including number of years in Canada and family functioning (i.e., PedsQL Family Impact Module). RESULTS: Sixteen percent of patients reported elevated social adjustment difficulties. Multiple linear regression found better family functioning [B = .48, t = 2.65, p = .016], and higher executive functioning [B = -.43, t = -2.39, p = .028] were related to higher scores on the PedsQL parent-proxy ratings of social adjustment [F(4,18) = 5.88, p = .003]. Male sex [B = .54, t = 3.08, p = .005], and having lived more years in Canada [B = .55, t = 2.81, p = .009], were related to higher PedsQL self-reported social adjustment [F(4,23) = 3.75, p = .017]. The model examining the BASC-3 withdrawal subscale was not statistically significant [F(4,16) = 1.63, p = .22]. IMPLICATIONS: Social adjustment in children diagnosed with SCD warrants future research to understand the influence of executive function, and non-disease-related factors, particularly focusing on sociocultural factors.


Asunto(s)
Anemia de Células Falciformes , Calidad de Vida , Niño , Humanos , Masculino , Femenino , Estudios Retrospectivos , Calidad de Vida/psicología , Ajuste Social , Anemia de Células Falciformes/psicología , Canadá , Padres/psicología , Encuestas y Cuestionarios
4.
Proc Natl Acad Sci U S A ; 120(44): e2314788120, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37871225

RESUMEN

Nitrogenase is an active target of heterologous expression because of its importance for areas related to agronomy, energy, and environment. One major hurdle for expressing an active Mo-nitrogenase in Escherichia coli is to generate the complex metalloclusters (P- and M-clusters) within this enzyme, which involves some highly unique bioinorganic chemistry/metalloenzyme biochemistry that is not generally dealt with in the heterologous expression of proteins via synthetic biology; in particular, the heterologous synthesis of the homometallic P-cluster ([Fe8S7]) and M-cluster core (or L-cluster; [Fe8S9C]) on their respective protein scaffolds, which represents two crucial checkpoints along the biosynthetic pathway of a complete nitrogenase, has yet to be demonstrated by biochemical and spectroscopic analyses of purified metalloproteins. Here, we report the heterologous formation of a P-cluster-containing NifDK protein upon coexpression of Azotobacter vinelandii nifD, nifK, nifH, nifM, and nifZ genes, and that of an L-cluster-containing NifB protein upon coexpression of Methanosarcina acetivorans nifB, nifS, and nifU genes alongside the A. vinelandii fdxN gene, in E. coli. Our metal content, activity, EPR, and XAS/EXAFS data provide conclusive evidence for the successful synthesis of P- and L-clusters in a nondiazotrophic host, thereby highlighting the effectiveness of our metallocentric, divide-and-conquer approach that individually tackles the key events of nitrogenase biosynthesis prior to piecing them together into a complete pathway for the heterologous expression of nitrogenase. As such, this work paves the way for the transgenic expression of an active nitrogenase while providing an effective tool for further tackling the biosynthetic mechanism of this important metalloenzyme.


Asunto(s)
Azotobacter vinelandii , Metaloproteínas , Nitrogenasa/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Fijación del Nitrógeno/genética , Oxidorreductasas/metabolismo , Metaloproteínas/metabolismo , Proteínas Bacterianas/metabolismo
5.
J Pediatr Psychol ; 48(12): 971-981, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-37579243

RESUMEN

OBJECTIVE: Little is known about the symptoms, signs, and management guidelines for children under the age of 6 years after they sustain a concussion. Caregivers of such young children may have unique concerns and encounter different challenges from those of school-age children given the distinctive developmental characteristics of the early childhood period. This study aimed to explore the experience of caregivers through semistructured interviews to inform clinical practice. METHODS: Fifty caregivers of children aged 6 months to 5.99 years were interviewed 3 months postinjury for this qualitative study to document their experience in relation to their child's accident, recovery, and healthcare provisions. RESULTS: Four main themes were identified: (1) visible changes associated with caregiver concerns, (2) a roller-coaster of emotions after the injury, (3) healthcare providers' role in addressing the need for reassurance, and (4) the need for better information after the injury. CONCLUSION: The findings provide critical insight into the unique experiences and information needs of caregivers of young children who sustain concussion. The challenges identified can inform healthcare professionals regarding the needs of caregivers after early concussion and contribute to building a knowledge base for the development of age-appropriate anticipatory guidance for caregiver mental health and child recovery.


Asunto(s)
Conmoción Encefálica , Cuidadores , Niño , Humanos , Preescolar , Cuidadores/psicología , Conmoción Encefálica/terapia , Atención a la Salud , Investigación Cualitativa , Emociones
6.
J Am Chem Soc ; 145(34): 18977-18991, 2023 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-37590931

RESUMEN

Fe K-edge X-ray absorption spectroscopy (XAS) has long been used for the study of high-valent iron intermediates in biological and artificial catalysts. 4p-mixing into the 3d orbitals complicates the pre-edge analysis but when correctly understood via 1s2p resonant inelastic X-ray scattering and Fe L-edge XAS, it enables deeper insight into the geometric structure and correlates with the electronic structure and reactivity. This study shows that in addition to the 4p-mixing into the 3dz2 orbital due to the short iron-oxo bond, the loss of inversion in the equatorial plane leads to 4p mixing into the 3dx2-y2,xy, providing structural insight and allowing the distinction of 6- vs 5-coordinate active sites as shown through application to the Fe(IV)═O intermediate of taurine dioxygenase. Combined with O K-edge XAS, this study gives an unprecedented experimental insight into the electronic structure of Fe(IV)═O active sites and their selectivity for reactivity enabled by the π-pathway involving the 3dxz/yz orbitals. Finally, the large effect of spin polarization is experimentally assigned in the pre-edge (i.e., the α/ß splitting) and found to be better modeled by multiplet simulations rather than by commonly used time-dependent density functional theory.


Asunto(s)
Electrónica , Hierro , Rayos X , Espectroscopía de Absorción de Rayos X , Teoría Funcional de la Densidad
7.
J Am Chem Soc ; 145(29): 16015-16025, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37441786

RESUMEN

Lytic polysaccharide monooxygenases (LPMOs) catalyze the degradation of recalcitrant carbohydrate polysaccharide substrates. These enzymes are characterized by a mononuclear Cu(I) active site with a three-coordinate T-shaped "His-brace" configuration including the N-terminal histidine and its amine group as ligands. This study explicitly investigates the electronic structure of the d10 Cu(I) active site in a LPMO using Kß X-ray emission spectroscopy (XES). The lack of inversion symmetry in the His-brace site enables the 3d/p mixing required for intensity in the Kß valence-to-core (VtC) XES spectrum of Cu(I)-LPMO. These Kß XES data are correlated to density functional theory (DFT) calculations to define the bonding, and in particular, the frontier molecular orbital (FMO) of the Cu(I) site. These experimentally validated DFT calculations are used to evaluate the reaction coordinate for homolytic cleavage of the H2O2 O-O bond and understand the contribution of this FMO to the low barrier of this reaction and how the geometric and electronic structure of the Cu(I)-LPMO site is activated for rapid reactivity with H2O2.


Asunto(s)
Peróxido de Hidrógeno , Oxigenasas de Función Mixta , Oxigenasas de Función Mixta/química , Polisacáridos/metabolismo , Dominio Catalítico , Espectrometría por Rayos X
8.
J Sch Health ; 93(12): 1099-1110, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37386759

RESUMEN

BACKGROUND: An estimated 1 in 5 adolescents have sustained a concussion in North America. Teachers and school administrators are responsible for implementing academic accommodations and other supports for optimal return to learn following a concussion. The primary objective of this study was to describe the prevalence and feasibility of providing academic accommodations to students following concussion from the perspectives of middle and high school teachers and school administrators. METHODS: A cross-sectional survey was administered to teachers and school administrators (grades 7-12) across Canada online via REDCap. Participants were recruited via word-of-mouth and social media sampling. Survey responses were analyzed descriptively using proportions. RESULTS: The survey was completed by 180 educators (138 teachers and 41 school administrators), of whom 86% had previously provided academic accommodations to students following concussion, and 96% agreed that students should have access to accommodations following concussion. Some accommodations (eg, breaks, extra time) were provided more often and were more feasible to provide than others (eg, no new learning, reduced bright light). Educators reported limited preparation time and limited school personnel support to assist students following concussion. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: The most feasible accommodations should be prioritized, ensuring students are supported within the school environment. CONCLUSIONS: Teachers and school administrators confirmed the importance of providing accommodations to students following concussion.


Asunto(s)
Conmoción Encefálica , Adolescente , Humanos , Estudios Transversales , Conmoción Encefálica/epidemiología , Estudiantes , Cognición , Política de Salud
9.
J Am Chem Soc ; 145(24): 13284-13301, 2023 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-37294874

RESUMEN

In multicopper oxidases (MCOs), the type 1 (T1) Cu accepts electrons from the substrate and transfers these to the trinuclear Cu cluster (TNC) where O2 is reduced to H2O. The T1 potential in MCOs varies from 340 to 780 mV, a range not explained by the existing literature. This study focused on the ∼350 mV difference in potential of the T1 center in Fet3p and Trametes versicolor laccase (TvL) that have the same 2His1Cys ligand set. A range of spectroscopies performed on the oxidized and reduced T1 sites in these MCOs shows that they have equivalent geometric and electronic structures. However, the two His ligands of the T1 Cu in Fet3p are H-bonded to carboxylate residues, while in TvL they are H-bonded to noncharged groups. Electron spin echo envelope modulation spectroscopy shows that there are significant differences in the second-sphere H-bonding interactions in the two T1 centers. Redox titrations on type 2-depleted derivatives of Fet3p and its D409A and E185A variants reveal that the two carboxylates (D409 and E185) lower the T1 potential by 110 and 255-285 mV, respectively. Density functional theory calculations uncouple the effects of the charge of the carboxylates and their difference in H-bonding interactions with the His ligands on the T1 potential, indicating 90-150 mV for anionic charge and ∼100 mV for a strong H-bond. Finally, this study provides an explanation for the generally low potentials of metallooxidases relative to the wide range of potentials of the organic oxidases in terms of different oxidized states of their TNCs involved in catalytic turnover.


Asunto(s)
Ceruloplasmina , Histidina , Ceruloplasmina/química , Ligandos , Cobre/química , Trametes , Electricidad Estática , Lacasa/metabolismo
10.
Clin J Sport Med ; 33(2): 130-138, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36731042

RESUMEN

OBJECTIVE: To examine the association between self-reported and parent-reported attention problems and hyperactivity and rates of injury and concussion in Canadian youth ice hockey players. DESIGN: Secondary analyses of 2 prospective cohort studies. SETTING: Canadian youth ice hockey teams. PARTICIPANTS: Ice hockey players (ages 11-17 years) were recruited by team, over 4 seasons (2011-2016). A combined 1709 players contributing 1996 player-seasons were analyzed (257 players participated in more than one season). ASSESSMENT OF RISK FACTORS: Data were collected from preseason baseline questionnaires, including child and parent proxy forms of the Behavior Assessment System for Children, second edition. MAIN OUTCOME MEASURES: Injury and concussion rates and incidence rate ratios (IRR) comparing players with and without self-identified or parent-identified attention problems and hyperactivity, adjusted for covariates (ie, body checking policy, previous injury/concussion, and age) and a random effect for team, were estimated using multiple multilevel negative binomial regression. RESULTS: When analyzed continuously, rates of concussion increased with higher self-reported and parent-reported measures of attention problems [IRR SELF = 1.025; 95% confidence interval (CI): 1.011-1.040; IRR PARENT = 1.032; 95% CI: 1.008-1.057]. Self-reported hyperactivity was significantly associated with concussion (IRR = 1.021; 95% CI: 1.007-1.035), but parent-reported hyperactivity was not (IRR = 1.005; 95% CI: 0.983-1.028). A T score ≥ 60 cutoff combining attention problems and hyperactivity scores (an estimate of probable attention-deficit hyperactivity disorder) was not significantly associated with rates of injury or concussion. CONCLUSIONS: Attention problems and hyperactivity may place youth ice hockey players at increased risk of concussion and injury. Preseason assessments could identify players for targeted concussion education and risk reduction strategies.


Asunto(s)
Traumatismos en Atletas , Conmoción Encefálica , Hockey , Niño , Humanos , Adolescente , Canadá/epidemiología , Estudios Prospectivos , Autoinforme , Hockey/lesiones , Factores de Riesgo , Conmoción Encefálica/complicaciones , Incidencia , Padres , Atención , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/etiología
11.
Pediatr Res ; 93(6): 1752-1764, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36085365

RESUMEN

BACKGROUND: We described longitudinal trends in the incidence of episodes of care (EOC) and follow-up care for pediatric concussion in relation to age, sex, rurality of patient residence, point of care, and area-based socioeconomic status (SES) in Alberta, Canada. METHODS: A retrospective population-based cohort study was conducted using linked, province-wide administrative health data for all patients <18 years of age who received a diagnosis of concussion, other specified injuries of head, unspecified injury of head, or post-concussion syndrome between April 1, 2004 and March 31, 2018. Data were geospatially mapped. RESULTS: Concussion EOCs increased 2.2-fold over the study period, follow-up visits 5.1-fold. Care was increasingly received in physician office (PO) settings. Concussion diagnoses in rural and remote areas occurred in emergency department (ED) settings more often than in metro centres or urban areas (76%/75% vs. 52%/60%). Proportion of concussion diagnoses was positively related to SES and age. Diagnosis and point of care varied geographically. CONCLUSIONS: The shift in care to PO settings, increased incidence of all diagnoses, and the higher use of the ED by some segments of the population all have important implications for appropriate clinical management and the efficient provision of health care for pediatric concussion. IMPACT: This is the first study to use EOC to describe longitudinal trends in incidence and follow-up care for pediatric concussion in relation to age, sex, rurality, point of care, and area-based SES. We report increased incidence of concussion in both emergency and outpatient settings and the proportion of diagnoses was positively related to SES and age. Patients increasingly received care for concussion in PO over time. Geospatial mapping indicated that the incidence of concussion and unspecified injury of head varied geographically and temporally. Results have important implications for appropriate clinical management and efficient provision of health care following pediatric concussion.


Asunto(s)
Conmoción Encefálica , Humanos , Niño , Alberta/epidemiología , Estudios Retrospectivos , Estudios de Cohortes , Incidencia , Conmoción Encefálica/diagnóstico , Conmoción Encefálica/epidemiología , Conmoción Encefálica/terapia , Atención a la Salud
12.
Hum Brain Mapp ; 44(4): 1711-1724, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36478489

RESUMEN

Developmental lateralization of brain function is imperative for behavioral specialization, yet few studies have investigated differences between hemispheres in structural connectivity patterns, especially over the course of development. The present study compares the lateralization of structural connectivity patterns, or topology, across children, adolescents, and young adults. We applied a graph theory approach to quantify key topological metrics in each hemisphere including efficiency of information transfer between regions (global efficiency), clustering of connections between regions (clustering coefficient [CC]), presence of hub-nodes (betweenness centrality [BC]), and connectivity between nodes of high and low complexity (hierarchical complexity [HC]) and investigated changes in these metrics during development. Further, we investigated BC and CC in seven functionally defined networks. Our cross-sectional study consisted of 211 participants between the ages of 6 and 21 years with 93% being right-handed and 51% female. Global efficiency, HC, and CC demonstrated a leftward lateralization, compared to a rightward lateralization of BC. The sensorimotor, default mode, salience, and language networks showed a leftward asymmetry of CC. BC was only lateralized in the salience (right lateralized) and dorsal attention (left lateralized) networks. Only a small number of metrics were associated with age, suggesting that topological organization may stay relatively constant throughout school-age development, despite known underlying changes in white matter properties. Unlike many other imaging biomarkers of brain development, our study suggests topological lateralization is consistent across age, highlighting potential nonlinear mechanisms underlying developmental specialization.


Asunto(s)
Encéfalo , Sustancia Blanca , Adulto Joven , Humanos , Niño , Adolescente , Femenino , Adulto , Masculino , Estudios Transversales , Encéfalo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética
13.
Int J Popul Data Sci ; 8(4): 2142, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38419825

RESUMEN

Introduction: Around the world, many organisations are working on ways to increase the use, sharing, and reuse of person-level data for research, evaluation, planning, and innovation while ensuring that data are secure and privacy is protected. As a contribution to broader efforts to improve data governance and management, in 2020 members of our team published 12 minimum specification essential requirements (min specs) to provide practical guidance for organisations establishing or operating data trusts and other forms of data infrastructure. Approach and Aims: We convened an international team, consisting mostly of participants from Canada and the United States of America, to test and refine the original 12 min specs. Twenty-three (23) data-focused organisations and initiatives recorded the various ways they address the min specs. Sub-teams analysed the results, used the findings to make improvements to the min specs, and identified materials to support organisations/initiatives in addressing the min specs. Results: Analyses and discussion led to an updated set of 15 min specs covering five categories: one min spec for Legal, five for Governance, four for Management, two for Data Users, and three for Stakeholder & Public Engagement. Multiple changes were made to make the min specs language more technically complete and precise. The updated set of 15 min specs has been integrated into a Canadian national standard that, to our knowledge, is the first to include requirements for public engagement and Indigenous Data Sovereignty. Conclusions: The testing and refinement of the min specs led to significant additions and improvements. The min specs helped the 23 organisations/initiatives involved in this project communicate and compare how they achieve responsible and trustworthy data governance and management. By extension, the min specs, and the Canadian national standard based on them, are likely to be useful for other data-focused organisations and initiatives.


Asunto(s)
Privacidad , Humanos , Estados Unidos , Canadá
14.
Front Hum Neurosci ; 16: 976013, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36337852

RESUMEN

Magnetic resonance imaging (MRI) can provide a number of measurements relevant to sport-related concussion (SRC) symptoms; however, most studies to date have used a single MRI modality and whole-brain exploratory analyses in attempts to localize concussion injury. This has resulted in highly variable findings across studies due to wide ranging symptomology, severity and nature of injury within studies. A multimodal MRI, symptom-guided region-of-interest (ROI) approach is likely to yield more consistent results. The functions of the cerebellum and basal ganglia transcend many common concussion symptoms, and thus these regions, plus the white matter tracts that connect or project from them, constitute plausible ROIs for MRI analysis. We performed diffusion tensor imaging (DTI), resting-state functional MRI, quantitative susceptibility mapping (QSM), and cerebral blood flow (CBF) imaging using arterial spin labeling (ASL), in youth aged 12-18 years following SRC, with a focus on the cerebellum, basal ganglia and white matter tracts. Compared to controls similar in age, sex and sport (N = 20), recent SRC youth (N = 29; MRI at 8 ± 3 days post injury) exhibited increased susceptibility in the cerebellum (p = 0.032), decreased functional connectivity between the caudate and each of the pallidum (p = 0.035) and thalamus (p = 0.021), and decreased diffusivity in the mid-posterior corpus callosum (p < 0.038); no changes were observed in recovered asymptomatic youth (N = 16; 41 ± 16 days post injury). For recent symptomatic-only SRC youth (N = 24), symptom severity was associated with increased susceptibility in the superior cerebellar peduncles (p = 0.011) and reduced activity in the cerebellum (p = 0.013). Fewer days between injury and MRI were associated with reduced cerebellar-parietal functional connectivity (p < 0.014), reduced activity of the pallidum (p = 0.002), increased CBF in the caudate (p = 0.005), and reduced diffusivity in the central corpus callosum (p < 0.05). Youth SRC is associated with acute cerebellar inflammation accompanied by reduced cerebellar activity and cerebellar-parietal connectivity, as well as structural changes of the middle regions of the corpus callosum accompanied by functional changes of the caudate, all of which resolve with recovery. Early MRI post-injury is important to establish objective MRI-based indicators for concussion diagnosis, recovery assessment and prediction of outcome.

15.
J Am Chem Soc ; 144(42): 19305-19316, 2022 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-36219763

RESUMEN

The direct conversion of methane to methanol would have a wide reaching environmental and industrial impact. Copper-containing zeolites can perform this reaction at low temperatures and pressures at a previously defined O2-activated [Cu2O]2+ site. However, after autoreduction of the copper-containing zeolite mordenite and removal of the [Cu2O]2+ active site, the zeolite is still methane reactive. In this study, we use diffuse reflectance UV-vis spectroscopy, magnetic circular dichroism, resonance Raman spectroscopy, electron paramagnetic resonance, and X-ray absorption spectroscopy to unambiguously define a mononuclear [CuOH]+ as the CH4 reactive active site of the autoreduced zeolite. The rigorous identification of a mononuclear active site allows a reactivity comparison to the previously defined [Cu2O]2+ active site. We perform kinetic experiments to compare the reactivity of the [CuOH]+ and [Cu2O]2+ sites and find that the binuclear site is significantly more reactive. From the analysis of density functional theory calculations, we elucidate that this increased reactivity is a direct result of stabilization of the [Cu2OH]2+ H-atom abstraction product by electron delocalization over the two Cu cations via the bridging ligand. This significant increase in reactivity from electron delocalization over a binuclear active site provides new insights for the design of highly reactive oxidative catalysts.


Asunto(s)
Zeolitas , Zeolitas/química , Cobre/química , Metano/química , Dominio Catalítico , Metanol/química , Ligandos , Modelos Moleculares , Oxígeno/química , Espectroscopía de Resonancia por Spin del Electrón , Cationes
16.
Brain Inj ; 36(10-11): 1228-1236, 2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-36099151

RESUMEN

OBJECTIVES: There is a growing demand for remote assessment options for measuring cognition after mild traumatic brain injury (mTBI). The current study evaluated the criterion validity of the Brief Test of Adult Cognition by Telephone (BTACT) in distinguishing between adults with mTBI and trauma controls (TC) who sustained injuries not involving the head or neck. METHODS: The BTACT was administered to the mTBI (n = 46) and TC (n = 35) groups at 1-2 weeks post-injury. Participants also completed the Rivermead Post Concussion Symptoms Questionnaire. RESULTS: The BTACT global composite score did not significantly differ between the groups (t(79) = -1.04, p = 0.30); the effect size was small (d = 0.23). In receiver operating characteristic curve analyses, the BTACT demonstrated poor accuracy in differentiating between the groups (AUC = 0.567, SE = 0.065, 95% CI [0.44, 0.69]). The BTACT's ability to discriminate between mTBI and TCs did not improve after excluding mTBI participants (n = 15) who denied ongoing cognitive symptoms (AUC = 0.567, SE = 0.072, 95% CI [0.43, 0.71]). CONCLUSIONS: The BTACT may lack sensitivity to subacute cognitive impairment attributable to mTBI (i.e., not explained by bodily pain, post-traumatic stress, and other nonspecific effects of injury).


Asunto(s)
Conmoción Encefálica , Disfunción Cognitiva , Adulto , Humanos , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico , Conmoción Encefálica/psicología , Pruebas Neuropsicológicas , Cognición , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Estudios Longitudinales
17.
CJEM ; 24(8): 876-884, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36107402

RESUMEN

OBJECTIVE: This study investigates whether acute treatment with ibuprofen, acetaminophen, or both is associated with resolution of headache or reduction of headache pain at 7 days post-concussion in children and youth. METHODS: A secondary analysis of the Predicting and Preventing Post-concussive Problems in Pediatrics (5P) prospective cohort study was conducted. Individuals aged 5-18 years with acute concussion presenting to nine Canadian pediatric emergency departments (ED) were enrolled from August 2013 to June 2015. The primary outcome was the presence of headache at 7 days, measured using the Post-Concussion Symptom Inventory. The association between acute administration of ibuprofen, acetaminophen, or both and headache presence at 7 days was investigated with propensity scores and adjusted multivariate regression models. RESULTS: 2277 (74.3%) of 3063 participants had headache upon ED presentation. Of these participants, 1543 (67.8%) received an analgesic medication before or during their ED visit [ibuprofen 754 (33.1%), acetaminophen 445 (19.5%), both 344 (15.1%); or no medication 734 (32.2%)]. Multivariate analysis pertained to 1707 participants with propensity scores based on personal characteristics and symptoms; 877 (51.4%) reported headache at 7 days post-concussion. No association emerged between treatment and presence of headache at 7 days [ibuprofen vs. untreated: (relative risk (RR) = 1.12 (95% CI 0.99,1.26); acetaminophen vs untreated RR = 1.02 (95% CI 0.87,1.22); both vs untreated RR = 1.02 (95% CI 0.86,1.18)]. CONCLUSIONS: Exposure to ibuprofen, acetaminophen, or both in the acute phase does not decrease the risk of headache at 7 days post-concussion. Non-opioid analgesics like ibuprofen or acetaminophen may be prescribed for short-term headache relief but clinicians need to be cautious with long-term medication overuse in those whose headache symptoms persist.


RéSUMé: OBJECTIF: Cette étude vise à déterminer si un traitement aigu à l'ibuprofène, à l'acétaminophène ou aux deux est associé à la résolution des maux de tête ou à la réduction de la douleur des maux de tête 7 jours après la commotion cérébrale chez les enfants et les adolescents. MéTHODES: Une analyse secondaire de l'étude de cohorte prospective Predicting and Preventing Post-concussive Problems in Pediatrics (5P) a été réalisée. Des personnes âgées de 5 à 18 ans souffrant d'une commotion cérébrale aiguë se présentant dans neuf services d'urgence pédiatriques (SU) canadiens ont été inscrites d'août 2013 à juin 2015. Le résultat primaire était la présence de maux de tête à 7 jours, mesurée à l'aide du Post-Concussion Symptom Inventory. L'association entre l'administration aiguë d'ibuprofène, d'acétaminophène ou des deux et la présence de maux de tête à 7 jours a été étudiée à l'aide de scores de propension et de modèles de régression multivariés ajustés. RéSULTATS: 2277 (74,3%) des 3063 participants avaient des maux de tête lors de la présentation aux urgences. Parmi ces participants, 1 543 (67,8%) ont reçu un médicament analgésique avant ou pendant leur visite aux urgences [ibuprofène 754 (33,1%), acétaminophène 445 (19,5%), les deux 344 (15,1%); ou aucun médicament 734 (32,2%)]. L'analyse multivariée a porté sur 1707 participants avec des scores de propension basés sur les caractéristiques personnelles et les symptômes; 877 (51,4%) ont signalé des maux de tête 7 jours après la commotion cérébrale. Aucune association n'est apparue entre le traitement et la présence de céphalées à 7 jours [ibuprofène vs non traité: (risque relatif (RR) = 1,12 (95%CI:0,99,1,26); acétaminophène vs non traité RR = 1,02 (95% IC: 0,87,1,22); les deux vs non traité RR = 1,02 (95% IC: 0,86,1,18)]. CONCLUSIONS: L'exposition à l'ibuprofène, à l'acétaminophène ou aux deux dans la phase aiguë ne diminue pas le risque de céphalées 7 jours après la commotion. Les analgésiques non opioïdes comme l'ibuprofène ou l'acétaminophène peuvent être prescrits pour soulager les maux de tête à court terme, mais les cliniciens doivent faire attention à la surconsommation de médicaments à long terme chez les personnes dont les symptômes de maux de tête persistent.


Asunto(s)
Acetaminofén , Conmoción Encefálica , Adolescente , Niño , Humanos , Acetaminofén/uso terapéutico , Ibuprofeno/uso terapéutico , Estudios Prospectivos , Canadá , Analgésicos , Conmoción Encefálica/complicaciones , Cefalea/tratamiento farmacológico
18.
Chembiochem ; 23(19): e202200384, 2022 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-35925843

RESUMEN

Nitrogenase employs a sophisticated electron transfer system and a Mo-Fe-S-C cofactor, designated the M-cluster [(cit)MoFe7 S9 C]), to reduce atmospheric N2 to bioaccessible NH3 . Previously, we have shown that the cofactor-free form of nitrogenase can be repurposed as a protein scaffold for the incorporation of a synthetic Fe-S cluster [Fe6 S9 (SEt)2 ]4- . Here, we demonstrate the utility of an asymmetric Mo-Fe-S cluster [Cp*MoFe5 S9 (SH)]3- as an alternative artificial cofactor upon incorporation into the cofactor-free nitrogenase scaffold. The resultant semi-artificial enzyme catalytically reduces C2 H2 to C2 H4 , and CN- into short-chain hydrocarbons, yet it is clearly distinct in activity from its [Fe6 S9 (SEt)2 ]4- -reconstituted counterpart, pointing to the possibility to employ molecular design and cluster synthesis strategies to further develop semi-artificial or artificial systems with desired catalytic activities.


Asunto(s)
Hidrocarburos , Nitrogenasa , Hidrocarburos/metabolismo , Nitrogenasa/metabolismo , Oxidación-Reducción
19.
J Inorg Biochem ; 233: 111837, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35550498

RESUMEN

Nitrogenase is a versatile metalloenzyme that reduces N2, CO and CO2 at its cofactor site. Designated the M-cluster, this complex cofactor has a composition of [(R-homocitrate)MoFe7S9C], and it is assembled through the generation of a unique [Fe8S9C] core prior to the insertion of Mo and homocitrate. NifB is a radical S-adenosyl-L-methionine (SAM) enzyme that is essential for nitrogenase cofactor assembly. This review focuses on the recent work that sheds light on the role of NifB in the formation of the [Fe8S9C] core of the nitrogenase cofactor, highlighting the structure, function and mechanism of this unique radical SAM methyltransferase.


Asunto(s)
Metaloproteínas , Nitrogenasa , Metiltransferasas , Molibdoferredoxina/química , Nitrogenasa/química , S-Adenosilmetionina/química
20.
Neuropsychol Rehabil ; 32(8): 1854-1867, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35475722

RESUMEN

Acquired brain injury (ABI) occurs commonly in young children. Despite this, the psychosocial implications of ABI in young children are not established, with little understood about the impacts on self-perception and self-esteem. In this study we investigated self-perception, self-esteem and behaviour of children with early ABI. Children with an ABI (n = 47) before six years were compared to 17 typically developing controls (TDCs) matched on demographics. Children were aged 6-12 years and completed the Harter Self-Perception Profile. One parent completed the Child Behavior Checklist. No differences for self-perception and self-esteem were found between the groups. Parents of children with an early ABI reported more internalizing and externalizing behaviours. Children with more externalizing behaviour and social skill problems had more negative self-perceptions. Interaction effects were seen between socioeconomic status (SES) and child self-perception and behaviour. Specifically, children from families of higher SES had a more positive perception of their appearance and children from lower SES backgrounds had more externalizing behaviours and social problems. The study suggests that the relationship between ABI and self-perception and self-esteem is complicated and that children with behavioural problems have lowered feelings of competence. SES has an important role in self-perception and behavioural outcomes.


Asunto(s)
Lesiones Encefálicas , Problema de Conducta , Lesiones Encefálicas/psicología , Niño , Preescolar , Humanos , Padres , Autoimagen , Clase Social
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