Advanced Magnetic Resonance Imaging Biomarkers of the Injured Spinal Cord: A Comparative Study of Imaging and Histology in Human Traumatic Spinal Cord Injury.

A significant problem in the diagnosis and management of traumatic spinal cord injury (tSCI) is the heterogeneity of secondary injury and the prediction of neurological outcome. Imaging biomarkers specific to myelin loss and inflammation after tSCI would enable detailed assessment of the pathophysiological processes underpinning secondary damage to the cord. Such biomarkers could be used to biologically stratify injury severity and better inform prognosis for neurological recovery. While much work has been done to establish magnetic resonance imaging (MRI) biomarkers for SCI in animal models, the relationship between imaging findings and the underlying pathology has been difficult to discern in human tSCI because of the paucity of human spinal cord tissue. We utilized post-mortem spinal cords from individuals who had a tSCI to examine this relationship by performing ex vivo MRI scans before histological analysis. We investigated the correlation between the histological distribution of myelin loss and inflammatory cells in the injured spinal cord and a number of myelin and inflammation-sensitive MRI measures: myelin water fraction (MWF), inhomogeneous magnetization transfer ratio (ihMTR), and diffusion tensor and diffusion kurtosis imaging-derived fractional anisotropy (FA) and axial, radial, and mean diffusivity (AD, RD, MD). The histological features were analyzed by staining with Luxol Fast Blue (LFB) for myelin lipids and Class II major histocompatibility complex (Class II MHC) and CD68 for microglia and macrophages. Both MWF and ihMTR were strongly correlated with LFB staining for myelin, supporting the use of both as biomarkers for myelin loss after SCI. A decrease in ihMTR was also correlated with the presence of Class II MHC positive immune cells. FA and RD correlated with both Class II MHC and CD68 and may therefore be useful biomarkers for inflammation after tSCI. Our work demonstrates the utility of advanced MRI techniques sensitive to biological tissue damage after tSCI, which is an important step toward using these MRI techniques in the clinic to aid in decision-making.

Regulation of stress granule formation in human oligodendrocytes.

Oligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to stress. Here we show SGs in OLs in active and inactive areas of MS lesions as well as in normal-appearing white matter. In cultures of primary human adult brain derived OLs, metabolic stress conditions induce transient SG formation in these cells. Combining pro-inflammatory cytokines, which alone do not induce SG formation, with metabolic stress results in persistence of SGs. Unlike sodium arsenite, metabolic stress induced SG formation is not blocked by the integrated stress response inhibitor. Glycolytic inhibition also induces persistent SGs indicating the dependence of SG formation and disassembly on the energetic glycolytic properties of human OLs. We conclude that SG persistence in OLs in MS reflects their response to a combination of metabolic stress and pro-inflammatory conditions.

WITHDRAWN: Evaluation of Fourier Transform Infrared spectroscopy (IR Biotyper) as a complement to Whole genome sequencing (WGS) to characterise Enterobacter cloacae , Citrobacter freundii and Klebsiella pneumoniae isolates recovered from hospital sinks.

The authors have withdrawn their manuscript due to becoming aware of methodology issues related to the curation of the training set used to determine cut-off values for Biotyper cluster assignation and lack of replicate measurements on different days for the isolates analysed. It is therefore unclear whether the conclusions of the manuscript are founded and no further work is possible to correct these issues as the instrument is no longer available to the authors. If you have any questions, please contact the corresponding author.

Ustekinumab as induction and maintenance therapy for ulcerative colitis - national extended follow-up and a review of the literature.

INTRODUCTION: Ustekinumab use in ulcerative colitis had shown low adverse event and high persistence rates to 3 years via the UNIFI long-term extension study. Outcomes beyond 3 years have not been previously described. We describe the safety signals of the entire UNIFI Australian population beyond 3 years. METHODS: This retrospective multicenter observational cohort study recruited from all Australian UNIFI centers. The primary outcome was safety via adverse events. Secondary outcomes included the clinical relapse rate on ustekinumab, and the need to switch from ustekinumab to an alternate agent. RESULTS: There were 14 patients [11 male, mean age 47 (±14) years], with a median diagnosis of 10.8 (±4.5) years prior to UNIFI enrollment. Median follow-up was 298 weeks (5.7 years) (Interquartile range (IQR): 220-311 weeks). Within the long-term extension, there were three serious adverse events and one minor event. 42.9% (6/14) patients had clinical relapses, of which clinical remission was recaptured in 83.3% (5/6). 85.7% (12/14) persisted on ustekinumab in the long-term, with 7.1% (1/14) electively ceasing ustekinumab and 7.1% (1/14) changed from ustekinumab due to clinical relapse. CONCLUSION: For moderate-to-severe UC in Australia, ustekinumab maintained efficacy beyond 3 years with a high persistence rate and no new safety signals. TRIAL REGISTRATION: The trial is registered at ANZCTR (identifier: ACTRN12622001332718).

A workflow for the detection of antibiotic residues, measurement of water chemistry and preservation of hospital sink drain samples for metagenomic sequencing.

BACKGROUND: Hospital sinks are environmental reservoirs that harbour healthcare-associated (HCA) pathogens. Selective pressures in sink environments, such as antibiotic residues, nutrient waste and hardness ions, may promote antibiotic resistance gene (ARG) exchange between bacteria. However, cheap and accurate sampling methods to characterize these factors are lacking. AIMS: To validate a workflow to detect antibiotic residues and evaluate water chemistry using dipsticks. Secondarily, to validate boric acid to preserve the taxonomic and ARG ('resistome') composition of sink trap samples for metagenomic sequencing. METHODS: Antibiotic residue dipsticks were validated against serial dilutions of ampicillin, doxycycline, sulfamethoxazole and ciprofloxacin, and water chemistry dipsticks against serial dilutions of chemical calibration standards. Sink trap aspirates were used for a 'real-world' pilot evaluation of dipsticks. To assess boric acid as a preservative of microbial diversity, the impact of incubation with and without boric acid at ∼22 °C on metagenomic sequencing outputs was evaluated at Day 2 and Day 5 compared with baseline (Day 0). FINDINGS: The limits of detection for each antibiotic were: 3 µg/L (ampicillin), 10 µg/L (doxycycline), 20 µg/L (sulfamethoxazole) and 8 µg/L (ciprofloxacin). The best performing water chemistry dipstick correctly characterized 34/40 (85%) standards in a concentration-dependent manner. One trap sample tested positive for the presence of tetracyclines and sulphonamides. Taxonomic and resistome composition were largely maintained after storage with boric acid at ∼22 °C for up to five days. CONCLUSIONS: Dipsticks can be used to detect antibiotic residues and characterize water chemistry in sink trap samples. Boric acid was an effective preservative of trap sample composition, representing a low-cost alternative to cold-chain transport.

The CALIPR framework for highly accelerated myelin water imaging with improved precision and sensitivity.

Quantitative magnetic resonance imaging (MRI) techniques are powerful tools for the study of human tissue, but, in practice, their utility has been limited by lengthy acquisition times. Here, we introduce the Constrained, Adaptive, Low-dimensional, Intrinsically Precise Reconstruction (CALIPR) framework in the context of myelin water imaging (MWI); a quantitative MRI technique generally regarded as the most rigorous approach for noninvasive, in vivo measurement of myelin content. The CALIPR framework exploits data redundancy to recover high-quality images from a small fraction of an imaging dataset, which allowed MWI to be acquired with a previously unattainable sequence (fully sampled acquisition 2 hours:57 min:20 s) in 7 min:26 s (4.2% of the dataset, acceleration factor 23.9). CALIPR quantitative metrics had excellent precision (myelin water fraction mean coefficient of variation 3.2% for the brain and 3.0% for the spinal cord) and markedly increased sensitivity to demyelinating disease pathology compared to a current, widely used technique. The CALIPR framework facilitates drastically improved MWI and could be similarly transformative for other quantitative MRI applications.

Sirtuins and Metabolism Biomarkers in Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: a Correlation Study with Clinical Outcomes and Cognitive Impairments.

Multiple sclerosis (MS) is a primary inflammatory demyelinating disease with different clinical courses and subtypes. The present study aimed to determine whether mitochondrial dysfunction and sirtuins 1 and 3, as metabolism and epigenetic modifying factors, might contribute to MS disease progression measured by physical disability and cognitive impairment.The volunteers (n = 20 controls, n = 59 MS) were recruited and assessed for cognitive function and disability scores; then, patients were clinically classified as relapsing-remitting (RR) in remission phase, RR in relapse phase, and secondary progressive MS. We measured sirtuin (SIRT) 1 and 3 levels, mitochondrial complex I, IV, aconitase, and α-ketoglutarate dehydrogenase (α-KGD) activity in the peripheral blood mononuclear cells (PBMCs). Furthermore, SIRT1, pyruvate, lactate, and cytochrome c (Cyt c) were determined in plasma. Finally, we performed postmortem tissue immunohistochemistry to assess the level of SIRT1 and SIRT3 in the brain lesions of patients with MS.Increased disability and cognitive impairment in patients were correlated. Plasma level of lactate showed a correlation with the disability in MS patients; moreover, a trend toward increased Cyt c plasma level was observed. Investigation of PBMCs exhibited decreased SIRT1 during the relapse phase along with a reduced complex IV activity in all MS subgroups. α-KGD activity was significantly increased in the RR-remission, and SIRT3 was elevated in RR-relapse group. This elevation correlated with disability and cognitive impairment. Finally, immunohistochemistry demonstrated increased levels of SIRT1 and 3 in the brain active lesion of patients with MS.Our data suggest that mitochondrial dysfunction and alteration in some epigenetics and metabolism modifying factors in the CNS and peripheral blood cells may contribute or correlate with MS progression.

Adaptation of land treadmill scoring system for underwater treadmill in dogs with thoracolumbar intervertebral disc extrusion.

The underwater treadmill (UWTM) is utilized in dogs recovering from thoracolumbar intervertebral disc extrusion (TL-IVDE). Gait scoring is validated for dogs with TL-IVDE walking on the land treadmill (LT) but has not been reported for the UWTM. Our objective was to investigate if LT gait analysis could be applied to the UWTM and if non-ambulatory dogs walking unassisted on the UWTM, at a standardized water level, would be more likely to generate gait scores compared to on the LT. This was a prospective, observational study in dogs with TL-IVDE managed surigcally. At 0, 2, 4, 8 and 12 weeks post-operatively, paired video footage of dogs walking on the LT and UWTM (water level at the greater trochanter) was used to generate 0-100 stepping (SS) and coordination (regularity index, RI) scores. Scores were compared between treadmill type and over time. Twenty dogs were enrolled and seventy-eight paired recordings were available for review. Median gait scores increased over time but did not differ by treadmill type (P = 0.262 for SS, P = 0.533 for RI). Combining SS and RI, more recordings received scores of 0 for the LT (n = 58/156; 37.2 %) compared to the UWTM (n = 44/156; 28.2 %; P = 0.043). Scores of 0, at visits when there was at least movement present at multiple joints, was more common on the LT (n = 11/108; 10.2 %) compared to the UWTM (n = 2/108, 1.9 %; P = 0.026). In dogs recovering from TL-IVDE, LT-based gait scoring was feasible in dogs walking on the UWTM and might complement other gait analysis methods, especially for non-ambulatory dogs.

Detection, survival, and persistence of Staphylococcus capitis NRCS-A in neonatal units in England.

BACKGROUND: The multidrug-resistant Staphylococcus capitis clone, NRCS-A, is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. AIM: To investigate the potential for S. capitis to colonize surfaces within NICUs. METHODS: Surface swabs were collected from four NICUs with and without known NRCS-A colonizations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole-genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. FINDINGS: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whereas S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for three days with minimal losses in viability (<0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. CONCLUSION: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment.

Evolving relationship of Nares Strait ice arches on sea ice along the Strait and the North Water, the Arctic's most productive polynya.

Nares Strait, the waterway that separates northwest Greenland from Ellesmere Island, is a major pathway along which sea ice leaves the Arctic, including the planet's oldest and thickest sea ice that is experiencing an accelerated loss. Ice arches that develop during the winter at the Strait's northern or southern terminus can remain stable for months at a time during which the transport of sea ice ceases. The Arctic's most productive polynya, the North Water (NOW) or Pikialasorsuaq (West Greenlandic for 'great upwelling') forms at the Strait's southern end. There is evidence that a warming climate and the concomitant thinning of Arctic sea ice is weakening the arches and it has been proposed that this may impact the stability of NOW and the complex ecosystem that it sustains. Here we employ a categorization of recent winters with respect to the presence or absence of ice arches to explore their impact on sea ice along the Strait and over the NOW. We find that winters during which a southern ice arch is absent are associated with a reduced and thinner ice cover along the Strait with ice conditions over the NOW similar to that during winters with a southern arch. In winters, without a southern arch, there is also an acceleration of the winds along the Strait that contributes to the presence of reduced ice cover. Ocean color remote sensing data suggests that current levels of primary productivity over the NOW are independent of the presence or absence of an ice arch. The results suggest more research is needed to assess the stability of the NOW, with respect to reduced ice cover and primary productivity, in a future where ice arches cease to form along Nares Strait.

Perceptions of friendship, peers and influence on adolescent smoking according to tobacco control context: a systematic review and meta-ethnography of qualitative research.

BACKGROUND: A relationship between smoking and interpersonal influences has been well established within the literature. There have been cultural shifts in denormalisation and a reduction in tobacco smoking in many countries. Hence there is a need to understand social influences on adolescents' smoking across smoking normalisation contexts. METHODS: The search was conducted in July 2019 and updated in March 2022 within 11 databases and secondary sources. Search terms included schools, adolescents, smoking, peers, social norms and qualitative research. Screening was conducted by two researchers independently and in duplicate. Study quality was assessed using the eight-item Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-centre) tool for the appraisal of qualitative studies. Results were synthesised using a meta-narrative lens for meta-ethnography and compared across smoking normalisation contexts. RESULTS: Forty one studies were included and five themes were developed, mapping onto the socio ecological model. The social processes by which adolescents take up smoking differed according to a mixture of school type, peer group structure and the smoking culture within the school, as well as the wider cultural context. Data available from smoking denormalised contexts, described changes in social interactions around smoking to cope with its stigmatisation. This was manifested through i) direct peer influence, whereby subtle techniques were employed, ii) group belonging whereby smoking was less likely to be seen as a key determinant of group membership and smoking was less commonly reported to be used as a social tool, and iii) popularity and identity construction, whereby smoking was perceived more negatively in a denormalised context, compared with a normalised context. CONCLUSIONS: This meta-ethnography is the first study to demonstrate, drawing on international data, that peer processes in adolescent smoking may undergo changes as smoking norms within society change. Future research should focus on understanding differences across socioeconomic contexts, to inform the adaptation of interventions.

A qualitative exploration of stakeholder perspectives on the implementation of a whole school approach to mental health and emotional well-being in Wales.

Early intervention to support mental health and well-being of school-aged children may be of significant benefit in preventing escalation of mental health problems in later life. While there are limitations to current understanding of the best ways for schools to support mental well-being, a whole school approach (WSA), involving all those who are part of the school system in creating and sustaining a supportive environment where health is prioritized, may be effective. This research explored stakeholder views of this approach, as part of a contract commissioned by the Welsh Government to conduct an evaluability assessment of a WSA. Semistructured focus groups and interviews were completed with stakeholders from the health and education sectors, as well as parents, to explore how a WSA may operate in a Welsh context and barriers and facilitators to potential implementation and outcomes. Findings suggest that existing pressures on schools may impact implementation of a WSA, with school staff already time poor and many staff experiencing their own mental well-being challenges. Implementation may be supported by clear guidance at local and national levels, funding for staff time and training and stakeholder involvement at all stages. Long-term monitoring and evaluation are also needed to understand system changes.

Measurement of SARS-CoV-2 in air and on surfaces in Scottish hospitals.

BACKGROUND: There are still uncertainties in our knowledge of the amount of SARS-CoV-2 virus present in the environment - where it can be found, and potential exposure determinants - limiting our ability to effectively model and compare interventions for risk management. AIM: This study measured SARS-CoV-2 in three hospitals in Scotland on surfaces and in air, alongside ventilation and patient care activities. METHODS: Air sampling at 200 L/min for 20 min and surface sampling were performed in two wards designated to treat COVID-19-positive patients and two non-COVID-19 wards across three hospitals in November and December 2020. FINDINGS: Detectable samples of SARS-CoV-2 were found in COVID-19 treatment wards but not in non-COVID-19 wards. Most samples were below assay detection limits, but maximum concentrations reached 1.7×103 genomic copies/m3 in air and 1.9×104 copies per surface swab (3.2×102 copies/cm2 for surface loading). The estimated geometric mean air concentration (geometric standard deviation) across all hospitals was 0.41 (71) genomic copies/m3 and the corresponding values for surface contamination were 2.9 (29) copies/swab. SARS-CoV-2 RNA was found in non-patient areas (patient/visitor waiting rooms and personal protective equipment changing areas) associated with COVID-19 treatment wards. CONCLUSION: Non-patient areas of the hospital may pose risks for infection transmission and further attention should be paid to these areas. Standardization of sampling methods will improve understanding of levels of environmental contamination. The pandemic has demonstrated a need to review and act upon the challenges of older hospital buildings meeting current ventilation guidance.

Tracking westerly wind directions over Europe since the middle Holocene.

The variability of the northern westerlies has been considered as one of the key elements for modern and past climate evolution. Their multiscale behavior and underlying control mechanisms, however, are incompletely understood, owing to the complex dynamics of Atlantic sea-level pressures. Here, we present a multi-annually resolved record of the westerly drift over the past 6,500 years from northern Italy. In combination with more than 20 other westerly-sensitive records, our results depict the non-stationary westerly-affected regions over mainland Europe on multi-decadal to multi-centennial time scales, showing that the direction of the westerlies has changed with respect to the migrations of the North Atlantic centers of action since the middle Holocene. Our findings suggest the crucial role of the migrations of the North Atlantic dipole in modulating the westerly-affected domain over Europe, possibly modulated by Atlantic Ocean variability.

Molecular-Modified Photocathodes for Applications in Artificial Photosynthesis and Solar-to-Fuel Technologies.

Nature offers inspiration for developing technologies that integrate the capture, conversion, and storage of solar energy. In this review article, we highlight principles of natural photosynthesis and artificial photosynthesis, drawing comparisons between solar energy transduction in biology and emerging solar-to-fuel technologies. Key features of the biological approach include use of earth-abundant elements and molecular interfaces for driving photoinduced charge separation reactions that power chemical transformations at global scales. For the artificial systems described in this review, emphasis is placed on advancements involving hybrid photocathodes that power fuel-forming reactions using molecular catalysts interfaced with visible-light-absorbing semiconductors.

International Spinal Cord Injury Biobank: A Biorepository and Resource for Translational Research.

Over the past few decades, tremendous advances have been made in our understanding of the biological changes underpinning the devastating impairment of traumatic spinal cord injury (SCI). Much of this scientific research has focused on animal models of SCI, and comparatively little has been done in human SCI, largely because biospecimens from human SCI patients are not readily available. This paucity of scientific enquiry in human SCI represents an important void in the spectrum of translational research, as biological differences between animal models and the human condition need to be considered in the pre-clinical development of therapeutic approaches. The International Spinal Cord Injury Biobank (ISCIB) is a multi-user biorepository with the mission of accelerating therapeutic development in traumatic SCI through improved biological understanding of human injury, and the vision of serving as a global research resource where human SCI biospecimens are shared with researchers around the world. Aligned with internationally recognized best practices, ISCIB's formal governance structure and standard operating procedures have earned it official biobank certification through the Canadian Tissue Repository Network. Herein, we describe the translational research gap that ISCIB is helping to fill; its structure, governance and certification; how data and samples are accrued, processed and stored; and finally, the process through which samples and data are shared with global researchers. The purpose of this paper describing ISCIB is to serve as an introductory guidance document for the wider community of SCI researchers. By helping researchers understand the contents of ISCIB and the process of accessing biospecimens, we seek to further ISCIB's vision as being a resource for human and translational research in SCI, with the ultimate goal of finding disease-modifying therapies for this disabling condition.

First experience of implementing Candida auris real-time PCR for surveillance in the UK: detection of multiple introductions with two international clades and improved patient outcomes.

BACKGROUND: Candida auris has been associated with rapid transmission and high mortality. A novel PCR-based surveillance programme was initiated at a London teaching hospital from January 2018. The results of this implementation until March 2019 are presented along with the clinical, transmission and phylogenetic characteristics encountered in that setting. METHODS: A real-time PCR assay for C. auris was developed, validated, and implemented for direct use on skin swabs and urine. Environmental swabs were also tested by PCR as an emergency outbreak-control measure. Clinical risk factors and outcomes of patients were determined. Environmental dispersal was assessed using 24 h settle plate cultures around nine colonized patients followed by air sampling around one colonized patient during high- and low-turbulence activities. Sequencing was performed using Illumina HiSeq and maximum likelihood phylogenies were constructed using rapid bootstrap analysis. RESULTS: Twenty-one C. auris colonized patients were identified. Median turnaround time of colonization detection reduced from 141 h (5.8 days) to approximately 24 h enabling rapid infection-control precautions. Settle plates detected 70-600 cfu/m2 around colonized patients over 24 h and air sampling suggested dispersal during turbulent activities. C. auris DNA was detected from 35.7% environmental swabs. Despite being in a high-risk setting, no patients developed invasive infection. Sequencing analysis of isolates from this centre identified two introductions of the South Asian (Clade I) and one of the South African (Clade III) strain. CONCLUSION: The PCR offers a rapid, scalable method of screening and supports clinical risk reduction in settings likely to encounter multiple introductions.

SWATH-MS identification of CXCL7, LBP, TGFß1 and PDGFRß as novel biomarkers in human systemic mastocytosis.

Mastocytosis is a rare myeloproliferative disease, characterised by accumulation of neoplastic mast cells in one or several organs. It presents as cutaneous or systemic. Patients with advanced systemic mastocytosis have a median survival of 3.5 years. The aetiology of mastocytosis is poorly understood, patients present with a broad spectrum of varying clinical symptoms that lack specificity to point clearly to a definitive diagnosis. Discovery of novel blood borne biomarkers would provide a tractable method for rapid identification of mastocytosis and its sub-types. Moving towards this goal, we carried out a clinical biomarker study on blood from twenty individuals (systemic mastocytosis: n = 12, controls: n = 8), which were subjected to global proteome investigation using the novel technology SWATH-MS. This identified several putative biomarkers for systemic mastocytosis. Orthogonal validation of these putative biomarkers was achieved using ELISAs. Utilising this workflow, we identified and validated CXCL7, LBP, TGFß1 and PDGF receptor-ß as novel biomarkers for systemic mastocytosis. We demonstrate that CXCL7 correlates with neutrophil count offering a new insight into the increased prevalence of anaphylaxis in mastocytosis patients. Additionally, demonstrating the utility of SWATH-MS for the discovery of novel biomarkers in the systemic mastocytosis diagnostic sphere.

Serum neurofilament light chain correlates with myelin and axonal magnetic resonance imaging markers in multiple sclerosis.

BACKGROUND: Neurofilaments are cytoskeletal proteins that are detectable in the blood after neuroaxonal injury. Multiple sclerosis (MS) disease progression, greater lesion volume, and brain atrophy are associated with higher levels of serum neurofilament light chain (NfL), but few studies have examined the relationship between NfL and advanced magnetic resonance imaging (MRI) measures related to myelin and axons. We assessed the relationship between serum NfL and brain MRI measures in a diverse group of MS participants. METHODS AND MATERIALS: 103 participants (20 clinically isolated syndrome, 33 relapsing-remitting, 30 secondary progressive, 20 primary progressive) underwent 3T MRI to obtain myelin water fraction (MWF), geometric mean T2 (GMT2), water content, T1; high angular resolution diffusion imaging (HARDI)-derived axial diffusivity (AD), radial diffusivity (RD), fractional anisotropy (FA); diffusion basis spectrum imaging (DBSI)-derived AD, RD, FA; restricted, hindered, water and fiber fractions; and volume measurements of normalized brain, lesion, thalamic, deep gray matter (GM), and cortical thickness. Multiple linear regressions assessed the strength of association between serum NfL (dependent variable) and each MRI measure in whole brain (WB), normal appearing white matter (NAWM) and T2 lesions (independent variables), while controlling for age, expanded disability status scale, and disease duration. RESULTS: Serum NfL levels were significantly associated with metrics of axonal damage (FA: R2WB-HARDI = 0.29, R2NAWM-HARDI = 0.31, R2NAWM-DBSI = 0.30, R2Lesion-DBSI = 0.31; AD: R2WB-HARDI=0.31), myelin damage (MWF: R2WB = 0.29, R2NAWM = 0.30, RD: R2WB-HARDI = 0.32, R2NAWM-HARDI = 0.34, R2Lesion-DBSI = 0.30), edema and inflammation (T1: R2Lesion = 0.32; GMT2: R2WB = 0.31, R2Lesion = 0.31), and cellularity (restricted fraction R2WB = 0.30, R2NAWM = 0.32) across the entire MS cohort. Higher serum NfL levels were associated with significantly higher T2 lesion volume (R2 = 0.35), lower brain structure volumes (thalamus R2 = 0.31; deep GM R2 = 0.33; normalized brain R2 = 0.31), and smaller cortical thickness R2 = 0.31). CONCLUSION: The association between NfL and myelin MRI markers suggest that elevated serum NfL is a useful biomarker that reflects not only acute axonal damage, but also damage to myelin and inflammation, likely due to the known synergistic myelin-axon coupling relationship.

Exploring the association between school-based peer networks and smoking according to socioeconomic status and tobacco control context: a systematic review.

BACKGROUND: Whilst prevalence of youth smoking in middle and high income countries has decreased, inequality has prevailed. The introduction of legislation regulating tobacco use in public spaces varies across countries, impacting the tobacco control context. Thus reviewing our knowledge of how social networks may influence smoking differently within different contexts is required to facilitate the development of context-specific interventions. METHODS: The search, conducted on 31st May 2019, included the following smoking-related terms; schools, adolescents, peers and social networks. Inclusion and exclusion criteria were applied throughout the title and abstract screening and full text screening. Quality assessment and synthesis followed. Studies were narratively synthesised to identify changes according to legislative context. This synthesis was conducted separately for findings relating to three categories: socioeconomic status; social selection and influence; and network position. RESULTS: Thirty studies were included. Differences in the relationship between network characteristics and smoking according to socioeconomic status were measured in five out of fifteen studies in Europe. Results varied across studies, with differences in network characteristics and their association with smoking varying both between schools of a differing and those of a similar socioeconomic composition. For studies conducted both before and after the introduction of comprehensive smoking legislation, the evidence for selection processes was more consistent than influence, which varied according to reciprocity. Findings showed that isolates were more likely to smoke and in-degree and out-degree centrality were related to smoking both before and after the introduction of legislation. The relationship between popularity and smoking was contingent on school level smoking prevalence in studies conducted before the introduction of legislation, but not after. CONCLUSIONS: Overall, effects according to socioeconomic status were underreported in the included studies and no consistent evidence of change after the introduction of a comprehensive smoking ban was observed. Further network analyses are required using more recent data to obtain a comprehensive understanding of how network processes may influence smoking differently according to socioeconomic status, and how adaptation could be used to enhance intervention effectiveness. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42019137358 .