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Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system. Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons. Despite the recognition of potential heterogeneity in mature oligodendrocyte function, a comprehensive summary of mature oligodendrocyte diversity is lacking. We delve into early 20 th -century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes. Indeed, recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences. Furthermore, modern molecular investigations, employing techniques such as single cell/nucleus RNA sequencing, consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region. Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis, Alzheimer's disease, and psychiatric disorders. Nevertheless, caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations. Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity. Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species, sex, central nervous system region, age, and disease, hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
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OBJECTIVES: To evaluate the complication rate, mortality rate and putative risk factors for cecal or colonic surgery in dogs. MATERIALS AND METHODS: A multi-institutional retrospective study including dogs that had undergone surgery that involved the cecum or the colon. Medical records from three referral hospitals were reviewed for patient demographics and clinical data. The association between putative risk factors and survival to discharge or complications was assessed using univariable and multivariable analysis. RESULTS: Seventy-nine dogs met the criteria to be included in this study. Fifty-five dogs had full thickness incision surgeries, while 24 dogs had partial thickness surgeries. The complication and mortality rates for full thickness and partial thickness cecal/colonic surgeries were not statistically different. The dehiscence rate of colonic anastomosis in this study was four of 47 (8.5%). On univariate analysis, performing full thickness procedures out of hours had an association with increased complications and mortality. On multivariable analysis, no factors were associated with survival to discharge or complications. There was no association of board-certified surgeon presence in surgery with complications or mortality. CLINICAL SIGNIFICANCE: The performance of full thickness cecal/colonic surgery is not associated with a statistically significant increased risk for complications or mortality compared to partial thickness procedures, with a possible increased risk of complications and mortality in full thickness procedures out of hours.
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This guidance document has been prepared on behalf of the International Council for Standardization in Haematology (ICSH). The aim of the document is to provide guidance and recommendations for the performance and interpretation of activated partial thromboplastin time (APTT) and prothrombin time (PT) plasma mixing tests in clinical laboratories in all regions of the world. The following areas are included in this document: preanalytical, analytical, postanalytical, and quality assurance considerations as they relate to the proper performance and interpretation of plasma mixing tests. The recommendations are based on good laboratory practice, published data in peer-reviewed literature, and expert opinion.
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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.
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Grânulos Citoplasmáticos , Esclerose Múltipla , Humanos , Grânulos Citoplasmáticos/metabolismo , Grânulos de Estresse , Oligodendroglia , Citocinas/metabolismo , Estresse Fisiológico , Esclerose Múltipla/metabolismoRESUMO
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.
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Biomarcadores , Imageamento por Ressonância Magnética , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Biomarcadores/análise , Biomarcadores/metabolismo , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Imagem de Tensor de Difusão/métodos , Bainha de Mielina/patologia , Bainha de Mielina/metabolismo , Idoso de 80 Anos ou mais , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Medula Espinal/metabolismoRESUMO
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).
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Colite Ulcerativa , Ustekinumab , Humanos , Masculino , Pessoa de Meia-Idade , Ustekinumab/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Seguimentos , Indução de Remissão , Austrália , Recidiva , Resultado do Tratamento , Estudos Observacionais como Assunto , Estudos Multicêntricos como AssuntoRESUMO
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.
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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 â¼22 °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 â¼22 °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.
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Antibacterianos , Ácidos Bóricos , Água , Humanos , Antibacterianos/farmacologia , Doxiciclina , Fluxo de Trabalho , Hospitais , Sulfametoxazol , Ampicilina , CiprofloxacinaRESUMO
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.
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Bainha de Mielina , Água , Humanos , Bainha de Mielina/patologia , Imageamento por Ressonância Magnética/métodos , Medula Espinal/diagnóstico por imagem , Encéfalo/diagnóstico por imagemRESUMO
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.
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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.
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Doenças do Cão , Deslocamento do Disco Intervertebral , Disco Intervertebral , Animais , Cães , Doenças do Cão/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/veterinária , Estudos Prospectivos , ÁguaRESUMO
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.
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Desinfetantes , Staphylococcus aureus Resistente à Meticilina , Sepse , Infecções Estafilocócicas , Staphylococcus capitis , Recém-Nascido , Humanos , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/microbiologia , Sepse/microbiologia , Unidades de Terapia Intensiva Neonatal , Desinfetantes/farmacologiaRESUMO
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.
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Ecossistema , Água , Camada de Gelo , Clima , Estações do Ano , Regiões ÁrticasRESUMO
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.
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Amigos , Controle do Tabagismo , Adolescente , Humanos , Fumar , Fumar Tabaco , Pesquisa Qualitativa , Antropologia CulturalRESUMO
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.
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Saúde Mental , Instituições Acadêmicas , Criança , Humanos , País de Gales , Grupos Focais , EmoçõesRESUMO
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.
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COVID-19 , SARS-CoV-2 , Humanos , RNA Viral , Tratamento Farmacológico da COVID-19 , HospitaisRESUMO
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.
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Clima , Vento , Europa (Continente) , Oceano Atlântico , ItáliaRESUMO
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.
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Fotossíntese , Energia Solar , Catálise , Luz , SemicondutoresRESUMO
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.
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Candidíase , Antifúngicos , Candida , Candida auris , Candidíase/diagnóstico , Candidíase/epidemiologia , Humanos , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Reino Unido/epidemiologiaRESUMO
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.