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Summary: Background: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130–140 mm Hg within 1 h; maintained for 72 h) or guideline-recommended (systolic target 150 mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30, 2018. Methods: All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36 h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24–36 h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with ClinicalTrials.gov, number NCT01422616. Findings: There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24–36 h. Mean achieved systolic blood pressures over 1–24 h were 141 mm Hg and 149 mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24–36 h (0.3 [IQR 0.0–16.6] in the intensive group and 0.9 [0.0–12.5] in the guideline group; log Δmean −0.17, 95% CI −0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses. Interpretation: Intensive blood pressure lowering treatment to a systolic target

This supplementary dataset is supportive of the randomized sham-controlled, double-blind, crossover clinical trial investigating polarity- and intensity-dependent effects of high-definition transcranial electrical stimulation (HD-tDCS) applied over the right temporo-parietal junction on mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally. Data of eleven healthy right-handed adults (6 women, 5 men; mean age 31 ± 5.6 years old) were analyzed for MCA-BFv, assessed using transcranial doppler ultrasound on the stimulated and the contralateral hemisphere concomitantly, during and after 3 blocks of 2 min HD-tDCS at 1, 2, and 3 mA. Participants received three electrical stimulation conditions (anode center, cathode center, and sham) randomly ordered across different days. The collected data is publicly available at Mendeley Data. This article and the data will inform future related investigations and safety analysis of transcranial non-invasive brain stimulation.

Mycobacterium abscessus is one of the most important nontuberculous mycobacteria that cause lung diseases. In vitro infection models developed to analyze the immune response are frequently based on the addition of mycobacteria to mononuclear cells or neutrophils from peripheral blood. An important requirement of these assays is that most cells phagocytose mycobacteria, only accomplished by using large multiplicities of infection (1 or more bacteria per cell) which may not adequately reflect the inhalation of a few mycobacteria by the host. We propose modifications that try to mimic some of the conditions in which immune cells deal with mycobacteria. For the preparation of the inoculum mycobacteria are grown in solid media followed by preparation to a single cell suspension. Multiplicities of infection (number of bacteria per cell) are below 0.01. Serum-free cellular media is used to allow the growth of M. abscessus. After several days of incubation Bacterial Colonies in Cellular Culture (BCCC) develop, which are enumerated directly under an inverted microscope. These colonies may represent biofilm formation during chronic infections. • Low multiplicity of infection (below 0.01 bacteria per cell) reflects more realistically conditions encountered by immune cells in the lungs. • The surface of mycobacteria prepared for infection assays that are grown in solid media are less affected than that of mycobacteria grown in liquid media with detergents. • Colony formation in the infected cells may reflect the aggregation and biofilm formation in the lungs during chronic infection.

When South Florida became a hot spot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists, and administrators who rapidly built a multiplatform, polymerase chain reaction- and serology-based detection program, established drive-through facilities, and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and multiple diagnostic laboratory companies, and government officials enabled us to implement both Food and Drug Administration authorized and laboratory-developed testing–based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity to testing hundreds of health care workers and patients daily, within 3 weeks. We believe our experience can inform the efforts of others when faced with a crisis situation.

The sustained increase in the prevalence of protein aggregation related diseases requires the development of feasible methods for the design of therapeutic alternatives. The procedure traditionally used for the search of drugs or therapeutic mutations includes in vitro experiments, designed to prevent the aggregation of model proteins, which are then complemented with cellular toxicity studies in vivo, slowing down the finding of solutions. To address this, we have developed a protocol that facilitates the search of molecules and anti-aggregation mutations since it allows to evaluate their therapeutic capabilities directly in in vivo experiments with the use of zebrafish early embryos. Avoiding the necessity of performing in vitro and in vivo procedures separately. Giving a more realistic method for the results interpretation.Zebrafish embryos were induced to produce intracellular aggregates of proteins by simple microinjections of known quantities of an aggregation prone protein previously labeled. The toxicity was evaluated by the survival of the embryos, while the formation of aggregates was quantified by fluorescence microscopy. The size distribution of the protein aggregates was revealed by means of ultracentrifuge sedimentation analysis.For the development of the present method, the human γ-tubulin protein was used as model protein, which generated intracellular aggregates in more than 60% of the injected embryos. To evaluate the method, a mutation was performed that altered the state of intracellular aggregation of γ-tubulin, obtaining a significant decrease in the amount and size of the intracellular aggregates. The present method can be used for any suitable intracellular aggregation protein model.The current method present important advantages such as:Easy induction of intracellular aggregates.Simple detection of intracellular protein aggregates through fluorescence microscopy and subcellular fractionation.Overall view of the effect of drugs or mutations by combining the toxicity, the development behavior and the size distribution of intracellular protein aggregates. Method name: Induction of protein aggregates in zebrafish early embryos by direct microinjection of denatured protein, Keywords: Intracellular protein aggregation, Zebrafish embryo, Mutant screening, Aggregate size distribution, Drug discovery, Protein aggregate induction

Hunting is one of the main threats to biodiversity due to its synergistic effect with other anthropogenic activities. Aversive hunting is a radical measure aimed at species considered threats to human health or goods. This practice has proved high impacts on wildlife. We quantified sighting and hunting of Beaded lizards and analyzed its relation with habitat disturbance through semi-structured interviews in seven localities. Sighting and hunting relation with habitat was analyzed individually using correlation tests and globally using discriminant function analysis. Hunting frequency is closed to 50% and justified on the potential direct threat of these species. Habitat structure explained sighting frequency but not hunting. Our study exposes that impact on Beaded lizards due to aversive hunting is high and that an education plan is required to decrease it; we also show the importance of habitat structure for the conservation of Beaded lizards.

Experimental infections of either cells or animals require the preparation of good quality inocula. Unfortunately, the important pulmonary pathogen Streptococcus pneumoniae is a fastidious microorganism that suffers an autolysis process when cultured in vitro. Supplementation of Todd–Hewitt broth with a biological buffer (20 mM Tris–HCl, pH = 7.8) promotes a six hours delay in the beginning of the autolysis process. Additional improvements include washing bacteria before freezing, avoiding manipulations after thawing, and the use of glycerol (70% of the frozen bacteria was viable after 28 weeks at −80 °C, and aliquots were highly homogeneous. We have tested their utility in a whole blood infection model and have found that human plasma exhibits a higher microbicidal activity than whole blood, a result that we have not found previously reported. Additionally, we have also observed significant variations in the antimicrobial activity against different strains, which might be related to their virulence.• Media culture buffering extends S. pneumoniae viability for 6 h. • Washing before freezing of single use aliquots minimizes manipulation after thawing. • Experimental infection with the frozen inocula has shown that plasma has higher bactericidal activity than blood.

Introducción: La peregrinación religiosa a Arabia Saudí o Hajj es un precepto básico en la doctrina islámica. Anualmente millones de peregrinos (un 5% procedente de la Unión Europea) se concentran en La Meca después del Ramadán, con los riesgos sanitarios que eso conlleva. Métodos: Estudio observacional y prospectivo de una cohorte de peregrinos atendidos en visita de actividades preventivas predesplazamiento en la Unidad de Salud Internacional Metropolitana Norte (Santa Coloma de Gramenet, Barcelona, España) durante 2009-2010. Resultados: Se valoraron 193 peregrinos (135 hombres, 69,9%), con una edad media (DE) de 37,1 (16,9) años. Eran inmigrantes 176 (91,2%), originarios de Pakistán (54,9%), Marruecos (29%), Bangladesh (4,1%) y otros (7,2%). Se desplazaban a Arabia Saudí por una media (DE) de 16,3 (9,2) días; optaban por la peregrinación larga (Hajj) 80 (41,5%) y por la corta (Umra) 113 (58,5%). Presentaban antecedentes patológicos 29 (15%). Se obtuvo una cobertura vacunal superior al 75% para tétanos-difteria, antineumocócica y antimeningocócica tetravalente, y sólo de un 70,4% para la antigripal. Presentaron algún problema de salud 41 (13,5%), el 61% de ellos síntomas de vías respiratorias. Los factores de riesgo independientemente relacionados con presentar enfermedades fueron los días de estancia (odds ratio [OR]=1,06; intervalo de confianza del 95% [IC95%]: 1,01-1,11) y realizar el Hajj frente a la Umra (OR=1,08; IC95%: 1,07-1,12). Conclusiones: Los peregrinos a Arabia Saudí procedentes de España son un colectivo fundamentalmente joven y sano. Presentaron un mayor número de enfermedades aquellos con estancias más largas.Introduction: Religious pilgrimage to Saudi Arabia, or Hajj, is a basic tenet of the Islamic doctrine and, after Ramadan, annually represents the largest human concentration (with up to 5% of from the EU) around the world. Such a gathering entails health risks. Methods: A prospective observational study was conducted of a cohort of pilgrims attended for pre-travel preventive activities in the North Metropolitan International Health Unit (Santa Coloma de Gramenet, Barcelona, Spain) from 2009-2010. Results: A total of 193 pilgrims were assessed and 135 (69.9%) were men. Their mean age (SD) was 37.1 (16.9) years. Among the pilgrims, 176 (91.2%) were immigrants, mainly from Pakistan (54.9%), Morocco (29%), Bangladesh (4.1%) or other countries (7.2%). The pilgrims stayed in Saudi Arabia a mean (SD) of 16.3 (9.2) days. Eighty (41.5%) opted for the 1 month-long pilgrimage (Hajj) and 113 (58.5%) for the shorter Umra. One or more pathological antecedent was recorded in 29 (15%). Vaccination coverage was >75% for tetanus-diphtheria, pneumococcal and quadrivalent meningitis but was only 70.4% for influenza. After returning, 41 (13.5%) pilgrims reported some health problem; of these, 61% were respiratory tract symptoms. The risk factors independently correlated with the presence of diseases was the number of days in Saudi Arabia (OR=1.06; 95% CI: 1.01-1.11) and taking part in the Hajj compared with the Umra (OR=1.08; 95% CI: 1.07-1.12). Conclusions: Religious pilgrims from Spain to Saudi Arabia are mainly young and healthy. Those with longer stays abroad contracted a higher number of diseases.

In this work a new proposal to improve the emission efficiency of air-borne ultrasonic transducers is introduced. A theoretical ultrasonic transducer design is studied using a piezoelectric membrane and a Helmholtz resonator with two acoustic ports. The resonator provides radiation in the acoustic ports in phase with that of the membrane. Several finite element simulations and experimental results are used to study the device. The finite element models were used to compare its behaviour with that of conventional vacuum-cavity transducers. These results show an improvement in the bandwidth reaching a quality factor value of 19. Furthermore, the experimental measurements were used to study the effects of the resonant cavity in the response. Several measurements for different cavity depths were performed. The results show an improvement of 25 dB in the emitted pressure through tuning the transducer.En este trabajo se presenta una nueva propuesta para mejorar la eficiencia de transductores ultrasónicos acoplados a aire. Para este estudio se ha empleado un diseño teórico de transductor ultrasónico que utiliza una membrana piezoeléctrica y un resonador de Helmholtz con dos puertos acústicos. El resonador hace que la radiación en los puertos acústicos se encuentre en fase con la producida por la membrana. Para estudiar el dispositivo se utilizaron resultados obtenidos mediante programas de elementos finitos y resultados experimentales. Por un lado, los modelos de elementos finitos se utilizaron para comparar el comportamiento del dispositivo con el de transductores convencionales con cavidades al vacío. Estos resultados indican una mejora en el ancho de banda alcanzando valores de factor de calidad de 19. Por otro lado, los resultados experimentales se emplearon para identificar los efectos de la cavidad resonante en el funcionamiento del dispositivo. Para ello se realizaron varias medidas utilizando ciertas profundidades de cavidad. Los resultados muestran una mejora de 25 dB al afinar el transductor utilizando la cavidad más apropiada.

Background: Trials of endovascular therapy for basilar artery occlusion, including vertebral occlusion extending into the basilar artery, have shown inconsistent results. We aimed to pool data to estimate safety and efficacy and to explore the benefit across pre-specified subgroups through individual patient data meta-analysis., Methods: VERITAS was a systematic review and meta-analysis that pooled patient-level data from trials that recruited patients with vertebrobasilar ischaemic stroke who were randomly assigned to treatment with either endovascular therapy or standard medical treatment alone. We included studies done between Jan 1, 2010, and Sept 1, 2023. The primary outcome was 90-day favourable functional status (modified Rankin Scale [mRS] score 0-3, with a score of 3 indicating moderate disability). Safety outcomes were symptomatic intracranial haemorrhage and 90-day mortality., Findings: We screened 934 titles and abstracts. Of these, seven (<1%) full texts were screened. We included four trials (ATTENTION, BAOCHE, BASICS, and BEST). The pooled data included 988 patients (556 [56%] in the intervention groups and 432 [44%] in the control groups; median age 67 years [IQR 58-74]; 686 (69%) were male and 302 (31%) were female). 904 (91%) patients were randomly assigned within 12 h of estimated stroke onset. Three RCTs were done in a Chinese population and one included European and Brazilian patients. The proportion of patients achieving favourable functional status was higher in the endovascular therapy than control group (90-day mRS score 0-3 in 251 [45%] participants vs 128 [30%]; adjusted common odds ratio 2·41 [95% CI 1·78-3·26]; p<0·0001). Endovascular therapy led to an increase in functional independence (mRS score 0-2 in 194 [35%] participants vs 89 [21%]; 2·52 [1·82-3·48]; p<0·0001) as well as a reduction in both the degree of overall disability (2·09 [1·61-2·71]; p<0·0001) and mortality (198 [36%] of 556 patients vs 196 [45%] of 432; 0·60 [0·45-0·80]; p<0·0001) at 90 days, despite higher rates of symptomatic intracranial haemorrhage (30 [5%] of 548 vs two [<1%] of 413; 11·98 [2·82-50·81]; p<0·0001). Heterogeneity of treatment effect was noted for baseline stroke severity (uncertain effect in baseline National Institutes of Health Stroke Scale <10) and occlusion site (greater benefit with more proximal occlusions) but not across subgroups defined by age, sex, baseline posterior circulation Alberta Stroke Program Early CT Score, presence of atrial fibrillation or intracranial atherosclerotic disease, and time from onset to imaging., Interpretation: VERITAS supports the robust benefit of endovascular therapy in patients with vertebrobasilar artery occlusion with moderate to severe symptoms, with approximately 2·5-times increased likelihood of achieving a favourable functional outcome. Despite a significant increase in symptomatic intracranial haemorrhage risk, endovascular therapy for vertebrobasilar artery occlusion was associated with a significant reduction in both overall disability and mortality. Although the benefit of endovascular therapy remains uncertain for patients vertebrobasilar artery occlusion presenting with mild stroke severity and extensive infarcts on neuroimaging, we found a significant clinical benefit across a range of patients with vertebrobasilar artery occlusion., Funding: None., Competing Interests: Declaration of interests RGN reports consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Hyperfine, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron; and stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, CrestecBio, Euphrates Vascular, Vesalio, Viz-AI, RapidPulse, and Perfuze. RGN is one of the Principal Investigators of the Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW) trial. Funding for this project is provided by Cerenovus. RGN is the Principal Investigator of the Combined Thrombectomy for Distal Medium Vessel Occlusion Stroke (DUSK) trial. Funding for this project is provided by Stryker Neurovascular. RGN is an investor in Viz-AI, Perfuze, Cerebrotech, Reist/Q'Apel Medical, Truvic, Tulavi Therapeutics, Vastrax, Piraeus Medical, Brain4Care, Quantanosis AI, and Viseon. TGJ is advisor and investor for Anaconda, Route92, Viz.ai, FreeOx, Blockade Medical, and Methinks. He received personal fees in his role on the data and safety monitoring board (DSMB) and steering committee from Cerenovus and on the screening committee for Contego Medical. He received stock as an advisory board member for Corindus. He received grant support for Medtronic and from Stryker Neurovascular in his capacity as principal investigator for DAWN and AURORA. FJAM reports consulting fees from Stryker, Microvention, and Balt. DWJD reports funding from the Dutch Heart Foundation, Netherlands Brain Foundation, the Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, Penumbra, Stryker, Medtronic, Thrombolytic Science, and Cerenovus (all unrestricted grants for research), paid to his institution. VP reports payment or honoraria for lectures, presentations or educational events from Boehringer Ingelheim, Daichii Sankyo, AstraZeneca, and Bristol Myers Squibb, and support for attending meetings or travel from NoNo (travel reimbursement). WHvZ reports speaker fees from Stryker, Cerenovus, Microvention, Medtronic, and Nicolab, and consulting fees from Philips, all paid to institution; chaired the DSMBs of WeTrust (Philips) and ANAIS (Anaconda), all paid to his institution. WHvZ chaired the DSMB of InExtremis (CHU Montpellier, Montpellier, France), for which no payment was received. PM reports consulting fees from Medtronic and steering committee fees from Penumbra, all paid to his institution. HJA reports consulting fees (speaker, Advisory Board, and Data Safety Board honoraria) from Boehringer Ingelheim, Roche, and Novo Nordisk. OMP-N reports fees from Bayer, Boehringer Ingelheim, Medtronic, and Pfizer. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Like other eukaryotes, insect genomes contain a large portion of repetitive sequences, particularly transposable elements and satellite DNAs. This review highlights key studies on repetitive DNAs and examines their structural, functional, and evolutionary impact on insect genomes. Repetitive sequences promote genetic diversification through mutations and large-scale rearrangements, playing a crucial role in shaping genomic architecture, aiding organismal adaptation, and driving speciation. We also explore the influence of repeats in genome size variation and species incompatibilities, along with their contribution to adaptive phenotypes and gene regulation. Studying repetitive DNA in insects not only provides insights into basic genomic features but also offers valuable information for conservation strategies, pest control, and advancements in genetics, ecology, and evolutionary biology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage., Methods: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed., Findings: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098)., Interpretation: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition., Funding: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China., Competing Interests: Declaration of interests LS reports funding from the Medical Research Council of the UK, Sichuan Credit Pharmaceutic, and Takeda China; and speaker fees from Takeda China. CSA has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the Medical Research Council of the UK, Penumbra, and Takeda China; is also the chair of the data and safety monitoring boards for several trials; is a board member of WHO; and is the Editor-in-Chief of Cerebrovascular Disease. CY has received funding from West China Hospital. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Since neuronal activity is coupled with neurovascular activity, we aimed to analyze the cerebral blood flow hemodynamics during and following high-definition transcranial direct current stimulation (HD-tDCS). We assessed the mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally using transcranial doppler ultrasound, during and after HD-tDCS, in eleven right-handed healthy adult participants (6 women, 5 men; mean age 31 ± 5.6 years old), with no evidence of brain or cardiovascular dysfunction. The HD-tDCS electrode montage was centered over the right temporo-parietal junction. The stimulation protocol comprised 3 blocks of 2 min at each current intensity (1, 2, and 3 mA) and an inter-stimulus interval of 5 min between blocks. Participants received three electrical stimulation conditions (anode center, cathode center, and sham) on three different days, with an interval of at least 24 h. Stimulation was well tolerated across HD-tDCS conditions tested, and the volunteers reported no significant discomfort related to stimulation. There was no significant difference in the right or the left MCA-BFv during or after the stimulation protocol across all stimulation conditions. We conclude that at a range of intensities, vascular reaction assessed using middle cerebral artery blood flow is not significantly altered during or after HD-tDCS both locally and remotely, which provides further evidence for the safety of HD-tDCS., Competing Interests: Declaration of interest The City University of New York has inventions on tES with MB as inventor. MB has equity in Soterix Medical and serves on the scientific advisory boards or has grants from Mecta, Halo Neuroscience, Boston Scientific and GlaxoSmithKline. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Uncertainty exists over the prognostic significance of low arterial oxygen saturation (SaO 2 ) in acute stroke. We aimed to determine the strength of association of SaO 2 and adverse outcomes among participants of the international Head Positioning in acute Stroke Trial (HeadPoST)., Methods: Post-hoc analyzes of HeadPoST, a pragmatic cluster-crossover randomized trial of lying flat versus sitting up head positioning in 11,093 patients (age ≥18 years) with acute stroke at 114 hospitals in 9 countries during 2015-2016. Associations of the lowest recorded SaO 2 level, as a continuous measure and as a cut-point for desaturation (SaO 2 <93%), in the first 24 h and clinical outcomes of death or dependency (modified Rankin scale [mRS] scores 3-6) and any serious adverse event (SAE) at 90 days, were assessed in generalized linear mixed models adjusted for baseline and in-hospital management confounders., Results: There was an inverse J-shaped association between SaO 2 and death or dependency, with a nadir for optimal outcome at 96-97%. Patients with SaO 2 desaturation were older, and had greater neurological impairment, premorbid disability and cardiorespiratory disease. Desaturation was not clearly associated with death or dependency (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 0.95-1.48) but was with SAEs (aOR 1.34, 95% CI 1.07-1.68), without heterogeneity by head position, cardiac-respiratory comorbidity, or other pre-specified subgroups., Conclusions: Any change in SaO 2 outside of 96-97% is associated with poorer outcome after acute stroke., Clinical Trial Registration: HeadPoST is registered at ClinicalTrials.gov (NCT02162017)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Access to acute stroke unit (ASU) care is known to vary worldwide. We aimed to quantify regional variations in the various components of ASU care., Method: Secondary analysis of the Head Positioning in acute Stroke Trial (HeadPoST), an international, multicentre, cluster crossover trial of head-up versus head-down positioning in 11,093 acute stroke patients at 114 hospitals in 9 countries. Patients characteristics and 11 standard components of processes of care were described according to ASU admission within and across four economically-defined regional groups (Australia/UK, China [includes Taiwan], India/Sri Lanka, and South America [Brazil/Chile/Colombia]). Variations in process of ASU care estimates were obtained in hierarchical mixed models, with adjustment for study design and potential patient- and hospital-level confounders., Results: Of 11,086 patients included in analyses, 59.7% (n = 6620) had an ASU admission. In China, India/Sri Lanka and South America, ASU patients were older, had greater neurological severity and more premorbid conditions than non-ASU patients. ASU patients were more likely to receive reperfusion therapy and multidisciplinary care within regions, but the components of care varied across regions. With Australia/UK as reference, patients in other regions had a lower probability of receiving reperfusion therapy, especially in India/Sri Lanka (adjusted odds ratio [aOR] 0.27, 95% confidence interval [CI] 0.12-0.63) and multidisciplinary care (mainly in formal dysphagia assessment, physiotherapy and occupational therapy)., Conclusion: There is significant variation in the components of stroke care across economically-defined regions of the world. Ongoing efforts are required to reduce disparities and optimise health outcomes, especially in resource poor areas., Clinical Trial Registration: HeadPoST is registered at ClinicalTrials.gov (NCT02162017)., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Systolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressure for optimal outcome is uncertain. We assessed intensive blood pressure lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischaemic stroke., Methods: We did an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients (age ≥18 years) with acute ischaemic stroke and systolic blood pressure 150 mm Hg or more, who were screened at 110 sites in 15 countries. Eligible patients were randomly assigned (1:1, by means of a central, web-based program) within 6 h of stroke onset to receive intensive (target systolic blood pressure 130-140 mm Hg within 1 h) or guideline (target systolic blood pressure <180 mm Hg) blood pressure lowering treatment over 72 h. The primary outcome was functional status at 90 days measured by shift in modified Rankin scale scores, analysed with unadjusted ordinal logistic regression. The key safety outcome was any intracranial haemorrhage. Primary and safety outcome assessments were done in a blinded manner. Analyses were done on intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01422616., Findings: Between March 3, 2012, and April 30, 2018, 2227 patients were randomly allocated to treatment groups. After exclusion of 31 patients because of missing consent or mistaken or duplicate randomisation, 2196 alteplase-eligible patients with acute ischaemic stroke were included: 1081 in the intensive group and 1115 in the guideline group, with 1466 (67·4%) administered a standard dose among the 2175 actually given intravenous alteplase. Median time from stroke onset to randomisation was 3·3 h (IQR 2·6-4·1). Mean systolic blood pressure over 24 h was 144·3 mm Hg (SD 10·2) in the intensive group and 149·8 mm Hg (12·0) in the guideline group (p<0·0001). Primary outcome data were available for 1072 patients in the intensive group and 1108 in the guideline group. Functional status (mRS score distribution) at 90 days did not differ between groups (unadjusted odds ratio [OR] 1·01, 95% CI 0·87-1·17, p=0·8702). Fewer patients in the intensive group (160 [14·8%] of 1081) than in the guideline group (209 [18·7%] of 1115) had any intracranial haemorrhage (OR 0·75, 0·60-0·94, p=0·0137). The number of patients with any serious adverse event did not differ significantly between the intensive group (210 [19·4%] of 1081) and the guideline group (245 [22·0%] of 1115; OR 0·86, 0·70-1·05, p=0·1412). There was no evidence of an interaction of intensive blood pressure lowering with dose (low vs standard) of alteplase with regard to the primary outcome., Interpretation: Although intensive blood pressure lowering is safe, the observed reduction in intracranial haemorrhage did not lead to improved clinical outcome compared with guideline treatment. These results might not support a major shift towards this treatment being applied in those receiving alteplase for mild-to-moderate acute ischaemic stroke. Further research is required to define the underlying mechanisms of benefit and harm resulting from early intensive blood pressure lowering in this patient group., Funding: National Health and Medical Research Council of Australia; UK Stroke Association; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Effects of conventional heating (CH) and microwave (MW) on the structure and activity of horseradish peroxidase (HRP) in buffer solution were studied. CH incubation between 30 and 45 °C increased activity of HRP, reaching 170% of residual activity (RA) after 4-6 h at 45 °C. CH treatment at 50 and 60 °C caused HRP inactivation: RA was 5.7 and 16.7% after 12 h, respectively. Secondary and tertiary HRP structural changes were analyzed by circular dichroism (CD) and intrinsic fluorescence emission, respectively. Under CH, activation of the enzyme was attributed to conformational changes in secondary and tertiary structures. MW treatment had significant effects on the residual activity of HRP. MW treatment at 45 °C/30W followed by CH treatment 45 °C regenerated the enzyme activity. The greatest loss in activity occurred at 60 °C/60 W/30 min (RA 16.9%); without recovery of the original activity. The inactivation of MW-treated HRP was related to the loss of tertiary structure, indicating changes around the tryptophan environment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Obstructive sleep apnea is frequent during the acute phase of stroke, and it is associated with poorer outcomes. A well-established relationship between supine sleep and obstructive sleep apnea severity exists in non-stroke patients. This study investigated the frequency of supine sleep and positional obstructive sleep apnea in patients with ischemic or hemorrhagic stroke., Methods: Patients who suffered their first acute stroke, either ischemic or hemorrhagic, were subjected to a full polysomnography, including the continuous monitoring of sleep positions, during the first night after symptom onset. Obstructive sleep apnea severity was measured using the apnea-hypopnea index, and the NIHSS measured stroke severity., Results: We prospectively studied 66 stroke patients. The mean age was 57.6 ± 11.5 years, and the mean body mass index was 26.5 ± 4.9. Obstructive sleep apnea (apnea-hypopnea index ≥5) was present in 78.8% of patients, and the mean apnea-hypopnea index was 29.7 ± 26.6. The majority of subjects (66.7%) spent the entire sleep time in a supine position, and positional obstructive sleep apnea was clearly present in the other 23.1% of cases. A positive correlation was observed between the NIHSS and sleep time in the supine position (r(s) = 0.5; p<0.001)., Conclusions: Prolonged supine positioning during sleep was highly frequent after stroke, and it was related to stroke severity. Positional sleep apnea was observed in one quarter of stroke patients, which was likely underestimated during the acute phase of stroke. The adequate positioning of patients during sleep during the acute phase of stroke may decrease obstructive respiratory events, regardless of the stroke subtype.

Antimicrobial activity in human monocytes infected with Mycobacterium tuberculosis has been difficult to demonstrate in vitro, and the molecular mechanisms allowing the bacteria to survive intracellularly are unknown. As a means to test the influence of bacterial products in the microbicidal activity of monocytes we have developed an infection model with Legionella pneumophila, which is killed by interferon gamma activated cells. We demonstrate that this model is useful because M. tuberculosis lysates inhibit one hundred fold the interferon gamma induced activity against L. pneumophila. Comparable degrees of inhibition are also detected when we use lysates from the less pathogenic Mycobacterium gordonae and the pathogenic Staphylococcus aureus, suggesting the participation of a common mechanism. This hypothesis is supported by the fact that the pattern of cytokine secretion is similar in all cases. A significant difference is, however, observed when we used lysates from the non-pathogenic Escherichia coli, which resulted in the recovery of low numbers of bacteria, probably because they induce the cell death of infected monocytes.