Sex-Stratified Genome-Wide Association Study in the Spanish Population Identifies a Novel Locus for Lacunar Stroke.

Background: Ischemic stroke (IS) represents a significant health burden globally, necessitating a better understanding of its genetic underpinnings to improve prevention and treatment strategies. Despite advances in IS genetics, studies focusing on the Spanish population and sex-stratified analyses are lacking.

Methods: A case-control genome-wide association study was conducted with 9081 individuals (3493 IS cases and 5588 healthy controls).

Site-selective template-directed synthesis of antibody Fc conjugates with concomitant ligand release.

Template-directed methods are emerging as some of the most effective means to conjugate payloads at selective sites of monoclonal antibodies (mAbs). We have previously reported a method based on an engineered Fc-III reactive peptide to conjugate a radionuclide chelator to K317 of antibodies with the concomitant release of the Fc-III peptide ligand. Here, our method was redesigned to target two lysines proximal to the Fc-III binding site, K248 and K439.

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.

Background And Objectives: COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.

Methods: This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection.

Brain atrophy pattern in de novo Parkinson's disease with probable RBD associated with cognitive impairment.

Rapid eye movement sleep behavior disorder (RBD) is associated with high likelihood of prodromal Parkinson's disease (PD) and is common in de novo PD. It is associated with greater cognitive impairment and brain atrophy. However, the relation between structural brain characteristics and cognition remains poorly understood.

Template directed synthesis of antibody Fc conjugates with concomitant ligand release.

Antibodies are an attractive therapeutic modality for cancer treatment as they allow the increase of the treatment response rate and avoid the severe side effects of chemotherapy. Notwithstanding the strong benefit of antibodies, the efficacy of anti-cancer antibodies can dramatically vary among patients and ultimately result in no response to the treatment. Here, we have developed a novel means to regioselectively label the Fc domain of any therapeutic antibody with a radionuclide chelator in a single step chemistry, with the aim to study by SPECT/CT imaging if the radiolabeled antibody is capable of targeting cancer cells .

Predictors of Atrial Fibrillation Development in Patients With Embolic Stroke of Undetermined Source: An Analysis of the RE-SPECT ESUS Trial.

Background: A proportion of patients with embolic stroke of undetermined source have silent atrial fibrillation (AF) or develop AF after the initial evaluation. Better understanding of the risk for development of AF is critical to implement optimal monitoring strategies with the goal of preventing recurrent stroke attributable to underlying AF. The RE-SPECT ESUS trial (Randomized, Double-Blind Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) provides an opportunity to assess predictors for developing AF and associated recurrent stroke.

Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome.

Background And Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSS - NIHSS = ΔNIHSS), to examine its relevance to AIS mechanisms and long-term outcomes.

The antitumour drug ABTL0812 impairs neuroblastoma growth through endoplasmic reticulum stress-mediated autophagy and apoptosis.

Neuroblastoma is the leading cause of cancer death in children aged 1 to 4 years. Particularly, five-year overall survival for high-risk neuroblastoma is below 50% with no curative options when refractory or relapsed. Most of current therapies target cell division and proliferation, thereby inducing DNA damage and programmed cell death.

Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke.

Background and Purpose- Immune cells play a key role in the first 24h poststroke (acute phase), being associated with stroke outcome. We aimed to find genetic risk factors associated with leukocyte counts during the acute phase of stroke. Methods- Ischemic stroke patients with leukocyte counts data during the first 24h were included.

Validation of a clinical-genetics score to predict hemorrhagic transformations after rtPA.

Objective: To validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke.

Methods: We enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.

Maps of Tethys' Thermophysical Properties.

On 11 April 2015 Cassini's Composite Infrared Spectrometer (CIRS) made a series of observations of Tethys' daytime anti-Saturn hemisphere over a nine-hour time period. During this time the sub-spacecraft position was remarkably stable (0.3° S to 3.

Urine Haptoglobin and Haptoglobin-Related Protein Predict Response to Spironolactone in Patients With Resistant Hypertension.

Resistant hypertension prevalence is progressively increasing, and prolonged exposure to suboptimal blood pressure control results in higher cardiovascular risk and end-organ damage. Among various antihypertensive agents, spironolactone seems the most effective choice to treat resistant hypertension once triple therapy including a diuretic fails. However success in blood pressure control is not guaranteed, adverse effects are not negligible, and no clinical tools are available to predict patient's response.

PATJ Low Frequency Variants Are Associated With Worse Ischemic Stroke Functional Outcome.

Rationale: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome.

Objective: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date.

Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke.

Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events.

Methods: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry.

Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible.

Combination of Thrombolysis and Statins in Acute Stroke Is Safe: Results of the STARS Randomized Trial (Stroke Treatment With Acute Reperfusion and Simvastatin).

Background And Purpose: The STARS trial (Stroke Treatment With Acute Reperfusion and Simvastatin) was conducted to demonstrate the efficacy and safety of simvastatin treatment in acute stroke.

Methods: STARS07 was a multicentre, phase IV, prospective, randomized, double-blind, placebo-controlled trial. Patients with Acute ischemic stroke recruited within 12 hours from symptom onset were randomized to oral simvastatin 40 mg or placebo, once daily for 90 days.

Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients.

Objectives: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance.

PPM1A Methylation Is Associated With Vascular Recurrence in Aspirin-Treated Patients.

Background And Purpose: Despite great efforts by pharmacogenetic studies, the causes of aspirin failure to prevent the recurrence of ischemic events remain unclear. Our aim was to study whether epigenetics could be associated with the risk of vascular recurrence in aspirin-treated stroke patients.

Methods: We performed an epigenetic joint analysis study in 327 patients treated with aspirin.

TRAF3 Epigenetic Regulation Is Associated With Vascular Recurrence in Patients With Ischemic Stroke.

Background And Purpose: Clopidogrel is one of the most used antiplatelet drugs in patients with cardiovascular disease. However, 16% to 50% of patients have a high on-clopidogrel platelet reactivity and an increased risk of ischemic events. The pathogenesis of high on-treatment platelet reactivity in patients with stroke is only partially explained by genetic variations.

Maternal Body Weight and Gestational Diabetes Differentially Influence Placental and Pregnancy Outcomes.

Context: Maternal obesity and gestational diabetes mellitus (GDM) can both contribute to adverse neonatal outcomes. The extent to which this may be mediated by differences in placental metabolism and nutrient transport remains to be determined.

Objective: Our objective was to examine whether raised maternal body mass index (BMI) and/or GDM contributed to a resetting of the expression of genes within the placenta that are involved in energy sensing, oxidative stress, inflammation, and metabolic pathways.

Plastidial Glycolytic Glyceraldehyde-3-Phosphate Dehydrogenase Is an Important Determinant in the Carbon and Nitrogen Metabolism of Heterotrophic Cells in Arabidopsis.

This study functionally characterizes the Arabidopsis (Arabidopsis thaliana) plastidial glycolytic isoforms of glyceraldehyde-3-phosphate dehydrogenase (GAPCp) in photosynthetic and heterotrophic cells. We expressed the enzyme in gapcp double mutants (gapcp1gapcp2) under the control of photosynthetic (Rubisco small subunit RBCS2B [RBCS]) or heterotrophic (phosphate transporter PHT1.2 [PHT]) cell-specific promoters.

[Hemichorea associated with cerebral toxoplasmosis and AIDS].

Only 12 AIDS cases with hemichorea were reported in the literature. We report the first case of hemichorea associated with AIDS and cerebral toxoplasmosis in our country. A 26-year-old man had 3 episodes of focal seizures on the left side with subsequent loss of consciousness.

Electrophysiological assessment of spinal cord lesions by means of transcranial cortical stimulation.

Central Motor Conduction Time (CMCT) was assessed in 30 healthy volunteers and 22 patients with spinal cord lesions due to compressive, degenerative and demyelinating disease. To obtain the CMCT, electrical Transcranial Stimulation and Percutaneous Spinal Stimulation or F wave calculations were employed. Pyramidal Tract (PT) conduction was always abnormal in the clinically impaired corticospinal tracts of all the studied patients.

Percutaneous cervical stimulation: effects on intraspinal structures.

Changes in the amplitude of motor evoked potentials (MEPs) from percutaneous cervical stimulation (PCS) obtained at rest in the thenar muscles, and smaller than 0.8 mV, were studied under 3 different experimental conditions. A significant enhancement was observed mainly with a conditioning subthreshold transcranial stimulus and when MEPs were obtained in coincidence with weak voluntary contraction of the target muscle.

Central motor conduction in ischaemic and hemorrhagic cerebral lesions.

Electrical Transcranial Cortical Stimulation was performed in 20 healthy volunteers and 14 patients having supra- or infratentorial vascular lesions. Central Conduction Time (CCT) in the Pyramidal Tract (PT) was calculated by subtraction of the Peripheral Conduction Time and the spinal synaptic delay to the Motor Evoked Potential (MEP) latency. Twelve out of fourteen patients showed prolonged MEP latencies or CCTs in the affected corporal segments.