Reperfusion Beyond 6 Hours Reduces Infarct Probability in Moderately Ischemic Brain Tissue

We aimed to examine perfusion changes between 3 and 6, and 6 and 24 hours after stroke onset and their impact on tissue outcome

Defining the Ischemic Penumbra Using Hyperacute Neuroimaging: Deriving Quantitative Ischemic Thresholds

Despite three decades of promise, a neuro-imaging biomarker capable of delineating the ischemic penumbra is yet to be definitively demonstrated. Much progress has been made, especially with MR imaging. However, in order to rigorously define an imaging biomarker of the ischemic penumbra, carefully designed studies which can derive ischemic thresholds using quantitative imaging parameters may be required. Two thresholds are of interest: one which distinguishes the ischemic core from penumbra, and another which distinguishes the penumbra from benign oligemia. In this review, we discuss one possible approach to define these thresholds by following tissue fate in the presence or absence of early reperfusion

Clinically Relevant Reperfusion in Acute Ischemic Stroke: MTT Performs Better than Tmax and TTP

While several MRI parameters are used to assess tissue perfusion during hyperacute stroke, it is unclear which is optimal for measuring clinically-relevant reperfusion. We directly compared MTT prolongation (MTTp), TTP, and time-to-maximum (Tmax) to determine which best predicted neurological improvement and tissue salvage following early reperfusion

Spinolaminar line test as a screening tool for C1 stenosis.

Study Design Retrospective cohort. Objective To clarify the sensitivity of C3–C2 spinolaminar line test as a screening tool for the stenosis of C1 space available for the cord (SAC). Methods Spine clinic records from April 2005 to August 2011 were reviewed. The C1 SAC was measured on lateral radiographs, and the relative positions between a C1 posterior arch and the C3–C2 spinolaminar line were examined and considered positive when the C1 ring lay ventral to the line. Computed tomography (CT) scans and magnetic resonance imaging (MRI) were utilized to measure precise diameters of C1 and C2 SAC and to check the existence of spinal cord compression. Results Four hundred eighty-seven patients were included in this study. There were 246 men and 241 women, with an average age of 53 years (range: 18 to 86). The mean SAC at C1 on radiographs was 21.2 mm (range: 13.5 to 28.2). Twenty-one patients (4.3%) were positive for the spinolaminar line test; all of these patients had C1 SAC of 19.4 mm or less. Eight patients (1.6%) had C1 SAC smaller than C2 on CT examination; all of these patients had a positive spinolaminar test, with high sensitivity (100%) and specificity (97%). MRI analysis revealed that two of the eight patients with a smaller C1 SAC had spinal cord compression at the C1 level. Conclusion Although spinal cord compression at the level of atlas without instability is a rare condition, the spinolaminar line can be used as a screening of C1 stenosis.OAIID:oai:osos.snu.ac.kr:snu2016-01/102/0000004226/3ADJUST_YN:NEMP_ID:A079510DEPT_CD:801FILENAME:2016_spinolaminar line test as a screening tool for c1 stenosis.pdfDEPT_NM:의학과CONFIRM:

Conversations on grief and hope: A collaborative autoethnographic account exploring the lifeworlds of international youth engaged with climate action

This paper explores the lifeworlds of international youth involved in climate and/or environmental social action, narratives that have been largely absent from a literature that has tended to focus on ‘traditional’ youth activists located in the urban Global North. Written as a novel collaborative autoethnography involving youth as co-authors, the paper a) collectively reflects on the stories of youth from different countries and cultures on their journeys towards climate action, and b) foregrounds an emotional framing to examine these experiences. The youth co-authors, whose experiences are the focus of this paper, form part of innovative international Youth Advisory Board, set up to provide peer support to youth new to climate and environmental social action, as part of our British Academy Youth Futures-funded participatory action research project. We examine the youth’s narratives exploring opportunities and barriers they have navigated, their inspirations and the intersections with a range of other socio-cultural factors

Leukocytes mediate disease pathogenesis in the Ndufs4(KO) mouse model of Leigh syndrome

Symmetric, progressive, necrotizing lesions in the brainstem are a defining feature of Leigh syndrome (LS). A mechanistic understanding of the pathogenesis of these lesions has been elusive. Here, we report that leukocyte proliferation is causally involved in the pathogenesis of LS. Depleting leukocytes with a colony-stimulating factor 1 receptor inhibitor disrupted disease progression, including suppression of CNS lesion formation and a substantial extension of survival. Leukocyte depletion rescued diverse symptoms, including seizures, respiratory center function, hyperlactemia, and neurologic sequelae. These data reveal a mechanistic explanation for the beneficial effects of mTOR inhibition. More importantly, these findings dramatically alter our understanding of the pathogenesis of LS, demonstrating that immune involvement is causal in disease. This work has important implications for the mechanisms of mitochondrial disease and may lead to novel therapeutic strategies

Combination of (M)DSC and surface analysis to study the phase behaviour and drug distribution of ternary solid dispersions

Purpose: Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix. Methods: MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed. Results: The distribution of the API in the ternary solid dispersions depended on formulation parameters. The extent of API surface coverage and therefore the distribution of the API over both polymeric phases differed significantly for the three formulations. Conclusions: Combining (M)DSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions

Portable Rabies Virus Sequencing in Canine Rabies Endemic Countries Using the Oxford Nanopore MinION

As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION’s potential for low-cost, high volume sequencing of pathogens in locations with limited resources

Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021

Background Osteoarthritis is the most common form of arthritis in adults, characterised by chronic pain and loss of mobility. Osteoarthritis most frequently occurs after age 40 years and prevalence increases steeply with age. WHO has designated 2021–30 the decade of healthy ageing, which highlights the need to address diseases such as osteoarthritis, which strongly affect functional ability and quality of life. Osteoarthritis can coexist with, and negatively effect, other chronic conditions. Here we estimate the burden of hand, hip, knee, and other sites of osteoarthritis across geographies, age, sex, and time, with forecasts of prevalence to 2050. Methods In this systematic analysis for the Global Burden of Disease Study, osteoarthritis prevalence in 204 countries and territories from 1990 to 2020 was estimated using data from population-based surveys from 26 countries for knee osteoarthritis, 23 countries for hip osteoarthritis, 42 countries for hand osteoarthritis, and US insurance claims for all of the osteoarthritis sites, including the other types of osteoarthritis category. The reference case definition was symptomatic, radiographically confirmed osteoarthritis. Studies using alternative definitions from the reference case definition (for example self-reported osteoarthritis) were adjusted to reference using regression models. Osteoarthritis severity distribution was obtained from a pooled meta-analysis of sources using the Western Ontario and McMaster Universities Arthritis Index. Final prevalence estimates were multiplied by disability weights to calculate years lived with disability (YLDs). Prevalence was forecast to 2050 using a mixed-effects model. Findings Globally, 595 million (95% uncertainty interval 535–656) people had osteoarthritis in 2020, equal to 7·6% (95% UI 6·8–8·4) of the global population, and an increase of 132·2% (130·3–134·1) in total cases since 1990. Compared with 2020, cases of osteoarthritis are projected to increase 74·9% (59·4–89·9) for knee, 48·6% (35·9–67·1) for hand, 78·6% (57·7–105·3) for hip, and 95·1% (68·1–135·0) for other types of osteoarthritis by 2050. The global age-standardised rate of YLDs for total osteoarthritis was 255·0 YLDs (119·7–557·2) per 100 000 in 2020, a 9·5% (8·6–10·1) increase from 1990 (233·0 YLDs per 100 000, 109·3–510·8). For adults aged 70 years and older, osteoarthritis was the seventh ranked cause of YLDs. Age-standardised prevalence in 2020 was more than 5·5% in all world regions, ranging from 5677·4 (5029·8–6318·1) per 100 000 in southeast Asia to 8632·7 (7852·0–9469·1) per 100 000 in high-income Asia Pacific. Knee was the most common site for osteoarthritis. High BMI contributed to 20·4% (95% UI –1·7 to 36·6) of osteoarthritis. Potentially modifiable risk factors for osteoarthritis such as recreational injury prevention and occupational hazards have not yet been explored in GBD modelling. Interpretation Age-standardised YLDs attributable to osteoarthritis are continuing to rise and will lead to substantial increases in case numbers because of population growth and ageing, and because there is no effective cure for osteoarthritis. The demand on health systems for care of patients with osteoarthritis, including joint replacements, which are highly effective for late stage osteoarthritis in hips and knees, will rise in all regions, but might be out of reach and lead to further health inequity for individuals and countries unable to afford them. Much more can and should be done to prevent people getting to that late stage

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead