Permeability of the blood-brain barrier through the phases of ischaemic stroke and relation with clinical outcome: protocol for a systematic review

Introduction: Ischaemic stroke is the most prevalent type of stroke and is characterised by a myriad of pathological events triggered by a vascular arterial occlusion. Disruption of the blood-brain barrier (BBB) is a key pathological event that may lead to fatal outcomes. However, it seems to follow a multiphasic pattern that has been associated with distinct biological substrates and possibly contrasting outcomes. Addressing the BBB permeability (BBBP) along the different phases of stroke through imaging techniques could lead to a better understanding of the disease, improved patient selection for specific treatments and development of new therapeutic modalities and delivery methods. This systematic review will aim to comprehensively summarise the existing evidence regarding the evolution of the BBBP values during the different phases of an acute ischaemic stroke and correlate this event with the clinical outcome of the patient. Methods and analysis: We will conduct a computerised search on Medline, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science. In addition, grey literature and ClinicalTrials.gov will be scanned. We will include randomised controlled trials, cohort, cross-sectional and case-controlled studies on humans that quantitatively assess the BBBP in stroke. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias of the selected studies. If possible, data will be combined in a quantitative meta-analysis following the guidelines provided by Cochrane Handbook for Systematic Reviews of Interventions. We will assess cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. Ethics and dissemination: Ethical approval is not needed. All data used for this work are publicly available. The result obtained from this work will be published in a peer-reviewed journal and disseminated in relevant conferences.info:eu-repo/semantics/publishedVersio

Diagnostic accuracy of CT angiography and CT perfusion imaging for detecting distal medium vessel occlusions: Protocol for a systematic review and meta-analysis

Background: Distal medium vessel occlusions (DMVOs) represent 25-40% of all acute ischemic strokes (AIS). DMVO clinical syndromes are heterogenous, but as eloquent brain regions are frequently involved, they are often disabling. Since current intravenous fibrinolytic therapies may fail to recanalize up to two-thirds of DMVOs, endovascular treatment is progressively being considered in this setting. Nevertheless, the optimal imaging method for diagnosis remains to be defined. Stroke centers that use computed tomography as a routine stroke imaging approach rely on either isolated computed tomography angiography (CTA) or combined perfusion (CTP) studies. Despite a simplified non-CTP-dependent approach seeming reasonable for large vessel occlusion AIS diagnosis, CTP may still hold advantages for DMVOs workup. Therefore, this systematic review aims to compare the diagnostic performance of CTA and CTP in detecting DMVOs. Methods: We will perform a systematic search in PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. In addition, grey literature and ClinicalTrials.gov will be scanned. We will include any type of study that presents data on the diagnostic accuracy of CTA and/or CTP for detecting DMVOs. Two authors will independently review retrieved studies, and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. Data will be combined in a quantitative meta-analysis following the guidelines provided by the Cochrane Handbook for Systematic Reviews of Interventions. We will assess cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Discussion: This will be the first systematic review and meta-analysis that compares two different imaging approaches for detecting DMVOs. This study may help to define optimal acute ischemic stroke imaging work-up. Trial registration: PROSPERO registration: CRD42022344006.info:eu-repo/semantics/publishedVersio

Avaliação toxicopatologica de biopesticidas: fungos e bactérias em roedores por via oral.

RESUMO: Fatores como infectividade, persistência e patogenicidade de biopesticidas em relação a organismos não alvo exigem estudos mais aprofundados e o estabelecimento de parâmetros para a análise de risco. Vários fungos e bactérias vêm sendo utilizados no controle de pragas agrícolas de diversas culturas. Os estudos toxicopatológicos a respeito do risco de um biopesticida são conduzidos com uma dose desafio que é maior do que aquela usada a campo. O trabalho tem como objetivo apresentar os resultados dos testes realizados no laboratório para os organismos avaliados. As linhagens testadas foram administradas em ratos, em suspensões de 108 esporos/ml pela via oral em 1,0 ml de suspensão. Foram utilizados três tratamentos para cada via: agente ativo, agente inativado e o veículo de administração do agente, como controle. Os animais foram observados diariamente, não havendo alterações clínicas ou quaisquer lesões em órgãos internos. Os animais foram também submetidos à necrópsia em intervalos sequenciais após a exposição na dependência do agente, com a retirada de fígado, rim, pulmão e fezes para verificar a presença do fungo nestes tecidos. Os órgãos, depois de pesados, foram homogeneizados, diluídos e plaqueados em meio BDA ou Nutrient Agar (NA). O protocolo utilizado se mostrou adequado para analisar a segurança de uso deste produto em relação a mamíferos

Kinetics of antibodies in sera, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infections

SummaryObjectivesThe kinetics of three serological markers (IgM, IgA, and IgG) in serum, saliva, and urine samples from adult patients with primary or secondary dengue infection were studied.DesignSerum, saliva, and urine samples were collected from 22 patients with clinical and confirmed dengue 3 virus infection during the outbreak in Havana City in 2001. They were tested by capture IgM (MAC-ELISA), IgA (AAC-ELISA), and IgE (EAC-ELISA) and IgG ELISA inhibition method (EIM) to detect specific dengue antibodies.ResultsSimilar kinetics were observed in IgM, IgA, and IgG antibodies in saliva and IgA and IgG in urine samples from secondary cases compared with kinetics in serum samples, although the values were lower. No IgG antibody was detected in saliva and urine samples in primary cases and IgM antibody was not detected in urine samples from either primary or secondary infection. All secondary cases were positive for IgG in saliva and urine samples at day 7. The kinetics of specific IgE antibodies in primary and secondary cases were different.ConclusionsThe kinetics of three serological markers (IgM, IgA, and IgG) in serum, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infection were studied for the first time, showing its behavior and usefulness in dengue virus diagnosis. The specific IgE could play a role as a serological marker in secondary infections

Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery

The blood-brain barrier (BBB) is a dynamic interface responsible for maintaining the central nervous system homeostasis. Its unique characteristics allow protecting the brain from unwanted compounds, but its impairment is involved in a vast number of pathological conditions. Disruption of the BBB and increase in its permeability are key in the development of several neurological diseases and have been extensively studied in stroke. Ischemic stroke is the most prevalent type of stroke and is characterized by a myriad of pathological events triggered by an arterial occlusion that can eventually lead to fatal outcomes such as hemorrhagic transformation (HT). BBB permeability seems to follow a multiphasic pattern throughout the different stroke stages that have been associated with distinct biological substrates. In the hyperacute stage, sudden hypoxia damages the BBB, leading to cytotoxic edema and increased permeability; in the acute stage, the neuroinflammatory response aggravates the BBB injury, leading to higher permeability and a consequent risk of HT that can be motivated by reperfusion therapy; in the subacute stage (1-3 weeks), repair mechanisms take place, especially neoangiogenesis. Immature vessels show leaky BBB, but this permeability has been associated with improved clinical recovery. In the chronic stage (>6 weeks), an increase of BBB restoration factors leads the barrier to start decreasing its permeability. Nonetheless, permeability will persist to some degree several weeks after injury. Understanding the mechanisms behind BBB dysregulation and HT pathophysiology could potentially help guide acute stroke care decisions and the development of new therapeutic targets; however, effective translation into clinical practice is still lacking. In this review, we will address the different pathological and physiological repair mechanisms involved in BBB permeability through the different stages of ischemic stroke and their role in the development of HT and stroke recovery.info:eu-repo/semantics/publishedVersio

Crystal Structure, Optical Second Harmonic Generation, Piezoelectricity and Pyroelectricity

Funding Information: This research was funded by Fundação para a Ciência e Tecnologia through FEDER (European Fund for Regional Development)-COMPETE-QREN-EU (ref. UID/FIS/04650/2013 and UID/FIS/04650/2019) and E-Field—“Electric-Field Engineered Lattice Distortions (E-FiELD) for optoelectronic devices”, ref. PTDC/NAN-MAT/0098/2020. C.S.B.G. acknowledges funding from Fundação para a Ciência e Tecnologia FCT/MCTES through projects UIDB/50006/2020, UIDP/50006/2020 and LA/P/0008/2020 of the Associate Laboratory for Green Chemistry—LAQV, UIDB/04378/2020, UIDP/04378/2020 and LA/P/0140/2020 of UCIBIO and Associate Laboratory i4HB, respectively. Funding Information: We acknowledge national funds (OE), through FCT − Fundação para a Ciência e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of article 23 of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. Publisher Copyright: © 2023 by the authors.A polymorph of glycyl-L-alanine HI.H2O is synthesized from chiral cyclo-glycyl-L-alanine dipeptide. The dipeptide is known to show molecular flexibility in different environments, which leads to polymorphism. The crystal structure of the glycyl-L-alanine HI.H2O polymorph is determined at room temperature and indicates that the space group is polar (P21), with two molecules per unit cell and unit cell parameters a = 7.747 Å, b = 6.435 Å, c = 10.941 Å, α = 90°, β = 107.53(3)°, γ = 90° and V = 520.1(7) Å3. Crystallization in the polar point group 2, with one polar axis parallel to the b axis, allows pyroelectricity and optical second harmonic generation. Thermal melting of the glycyl-L-alanine HI.H2O polymorph starts at 533 K, close to the melting temperature reported for cyclo-glycyl-L-alanine (531 K) and 32 K lower than that reported for linear glycyl-L-alanine dipeptide (563 K), suggesting that although the dipeptide, when crystallized in the polymorphic form, is not anymore in its cyclic form, it keeps a memory of its initial closed chain and therefore shows a thermal memory effect. Here, we report a pyroelectric coefficient as high as 45 µC/m2K occurring at 345 K, one order of magnitude smaller than that of semi-organic ferroelectric triglycine sulphate (TGS) crystal. Moreover, the glycyl-L-alanine HI.H2O polymorph displays a nonlinear optical effective coefficient of 0.14 pm/V, around 14 times smaller than the value from a phase-matched inorganic barium borate (BBO) single crystal. The new polymorph displays an effective piezoelectric coefficient equal to (Formula presented.), when embedded into electrospun polymer fibers, indicating its suitability as an active system for energy harvesting.publishersversionpublishe

Effect of Myostatin Depletion on Weight Gain, Hyperglycemia, and Hepatic Steatosis during Five Months of High-Fat Feeding in Mice

The marked hypermuscularity in mice with constitutive myostatin deficiency reduces fat accumulation and hyperglycemia induced by high-fat feeding, but it is unclear whether the smaller increase in muscle mass caused by postdevelopmental loss of myostatin activity has beneficial metabolic effects during high-fat feeding. We therefore examined how postdevelopmental myostatin knockout influenced effects of high-fat feeding. Male mice with ubiquitous expression of tamoxifen-inducible Cre recombinase were fed tamoxifen for 2 weeks at 4 months of age. This depleted myostatin in mice with floxed myostatin genes, but not in control mice with normal myostatin genes. Some mice were fed a high-fat diet (60% of energy) for 22 weeks, starting 2 weeks after cessation of tamoxifen feeding. Myostatin depletion increased skeletal muscle mass ∼30%. Hypermuscular mice had ∼50% less weight gain than control mice over the first 8 weeks of high-fat feeding. During the subsequent 3 months of high-fat feeding, additional weight gain was similar in control and myostatin-deficient mice. After 5 months of high-fat feeding, the mass of epididymal and retroperitoneal fat pads was similar in control and myostatin-deficient mice even though myostatin depletion reduced the weight gain attributable to the high-fat diet (mean weight with high-fat diet minus mean weight with low-fat diet: 19.9 g in control mice, 14.1 g in myostatin-deficient mice). Myostatin depletion did not alter fasting blood glucose levels after 3 or 5 months of high-fat feeding, but reduced glucose levels measured 90 min after intraperitoneal glucose injection. Myostatin depletion also attenuated hepatic steatosis and accumulation of fat in muscle tissue. We conclude that blocking myostatin signaling after maturity can attenuate some of the adverse effects of a high-fat diet

Mejoras operativas en la valoración genética del ganado caprino lechero de raza murciano-granadina

Se compararon diferentes modelos para la evaluación de cabras lecheras para su uso en un programa de mejora genética establecido entre la Asociación de Ganaderos de Caprino de Raza Murciano-Granadina de la Comunidad Valenciana y el Centro de Investigación y Tecnología Animal del Instituto Valenciano de Investigaciones Agrarias. Se compararon en primer lugar dos modelos mixtos con diferente estructura de covarianzas. También se realizaron comparaciones entre modelos que incluyeron otros efectos sistemáticos: edad de la hembra en el momento del parto y días desde el parto hasta el primer control de la lactación. Se consideraron los caracteres estandarizados producción de leche y porcentajes de grasa y proteína. Las comparaciones se realizaron considerando criterios estadísticos de información. Los resultados indican que el modelo de repetibilidad es el más adecuado al tener en cuenta las covarianzas entre medidas de una cabra. La inclusión del efecto edad de la hembra al parto sólo fue ventajosa para el carácter producción de leche. La consideración del efecto tiempo desde el parto al primer control lechero fue positiva para los caracteres de producción de leche y de porcentaje de proteína. Ninguno de los efectos incluidos mejoró el modelo actualmente utilizado para porcentaje de grasa

Relationship between cognition and age at onset of first-episode psychosis: comparative study between adolescents, young adults, and adults

Psychotic disorders typically manifest from late adolescence to early adulthood, and an earlier onset might be associated with greater symptom severity and a worse long-term prognosis. This study aimed to compare the cognitive characteristics of patients with first-episode psychosis (FEP) by their age at onset. We included 298 patients diagnosed with FEP and classified them as having an early onset (EOS), youth onset (YOS), or adult onset (AOS) based on age limits of = 25 years (N = 116), respectively. Socio-demographic and clinical variables included age at baseline, gender, socio-economic status, antipsychotic medication, DSM-IV diagnoses assessed by clinical semi-structured interview, psychotic symptom severity, and age at onset. Neuropsychological assessment included six cognitive domains: premorbid intelligence, working memory, processing speed, verbal memory, sustained attention, and executive functioning. The EOS group had lower scores than the YOS or AOS groups in global cognition, executive functioning, and sustained attention. Although the scores in the YOS group were intermediate to those in the EOS and AOS groups for most cognitive factors, no statistically significant differences were detected between the YOS and AOS groups. Age at onset results in specific patterns of cognitive interference. Of note, impairment appears to be greater with EOS samples than with either YOS or AOS samples. A longitudinal study with a larger sample size is needed to confirm our findings

The role of premorbid iq and age of onset as useful predictors of clinical, functional outcomes, and recovery of individuals with a first episode of psychosis

Background: premorbid IQ (pIQ) and age of onset are predictors of clinical severity and long-term functioning after a first episode of psychosis. However, the additive influence of these variables on clinical, functional, and recovery rates outcomes is largely unknown. Methods: we characterized 255 individuals who have experienced a first episode of psychosis in four a priori defined subgroups based on pIQ (low pIQ < 85; average pIQ = 85) and age of onset (early onset < 18 years; adult onset = 18 years). We conducted clinical and functional assessments at baseline and at two-year follow-up. We calculated symptom remission and recovery rates using the Positive and Negative Symptoms of Schizophrenia Schedule (PANSS) and the Global Assessment Functioning (GAF or Children-GAF). We examined clinical and functional changes with pair-wise comparisons and two-way mixed ANOVA. We built hierarchical lineal and logistic regression models to estimate the predictive value of the independent variables over functioning or recovery rates. Results: early-onset patients had more severe positive symptoms and poorer functioning than adult-onset pa-tients. At two-year follow-up, only early-onset with low pIQ and adult-onset with average pIQ subgroups differed consistently, with the former having more negative symptoms (d = 0.59), poorer functioning (d = 0.82), lower remission (61% vs. 81.1%), and clinical recovery (34.1% vs. 62.2%). Con-clusions: early-onset individuals with low pIQ may present persistent negative symptoms, lower functioning, and less recovery likelihood at two-year follow-up. Intensive cognitive and functional programs for these individuals merit testing to improve long-term recovery rates in this subgroup. © 2021 by the authors. Licensee MDPI, Basel, Switzerland