Loss of nuclear DNA ligase III reverts PARP inhibitor resistance in BRCA1/53BP1 double-deficient cells by exposing ssDNA gaps.

Inhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, preclinical and clinical research with PARPi has revealed multiple resistance mechanisms, highlighting the need for identification of novel functional biomarkers and combination treatment strategies. Functional genetic screens performed in cells and organoids that acquired resistance to PARPi by loss of 53BP1 identified loss of LIG3 as an enhancer of PARPi toxicity in BRCA1-deficient cells. Enhancement of PARPi toxicity by LIG3 depletion is dependent on BRCA1 deficiency but independent of the loss of 53BP1 pathway. Mechanistically, we show that LIG3 loss promotes formation of MRE11-mediated post-replicative ssDNA gaps in BRCA1-deficient and BRCA1/53BP1 double-deficient cells exposed to PARPi, leading to an accumulation of chromosomal abnormalities. LIG3 depletion also enhances efficacy of PARPi against BRCA1-deficient mammary tumors in mice, suggesting LIG3 as a potential therapeutic target.

rAAV-compatible human mini promoters enhance transgene expression in rat retinal ganglion cells.

Recombinant adeno-associated viral vectors (rAAV) are the safest and most effective gene delivery platform to drive the treatment of many inherited eye disorders in well-characterized animal models. The use in rAAV of ubiquitous promoters derived from viral sequences such as CMV/CBA (chicken ß-actin promoter with cytomegalovirus enhancer) can lead to unwanted side effects such as pro-inflammatory immune responses and retinal cytotoxicity, thus reducing therapy efficacy. Thus, an advance in gene therapy is the availability of small promoters, that potentiate and direct gene expression to the cell type of interest, with higher safety and efficacy. In this study, we used six human mini-promoters packaged in rAAV2 quadruple mutant (Y-F) to test for transduction of the rat retina after intravitreal injection. After four weeks, immunohistochemical analysis detected GFP-labeled cells in the ganglion cell layer (GCL) for all constructs tested. Among them, Ple25sh1, Ple25sh2 and Ple53 promoted a widespread reporter-transgene expression in the GCL, with an increased number of GFP-expressing retinal ganglion cells when compared with the CMV/CBA vector. Moreover, Ple53 provided the strongest levels of GFP fluorescence in both cell soma and axons of retinal ganglion cells (RGCs) without any detectable adverse effects in retina function. Remarkably, a nearly 50-fold reduction in the number of intravitreally injected vector particles containing Ple53 promoter, still attained levels of transgene expression similar to CMV/CBA. Thus, the tested MiniPs show great potential for protocols of retinal gene therapy in therapeutic applications for retinal degenerations, especially those involving RGC-related disorders such as glaucoma.

New insights about the toxicity of 2,4-D: Gene expression analysis reveals modulation on several subcellular responses in Chironomus riparius.

Herbicides are the main class of pesticides applied in crops and are capable of polluting the surrounding freshwater system; thus, understanding their impact on non-target species, whose mechanism of action is not described, helps to elucidate the real risks of these pollutants to the environment. 2,4-dichlorophenoxyacetic acid (2,4-D) is frequently detected in water and, due to its persistence, poses a risk to wildlife. In this way, the present work aimed to describe the implication of exposure to concentrations of 2,4-D already reported in aquatic environments in several physiological mechanisms of C. riparius at molecular and biochemical levels. To achieve this, bioassays were conducted with fourth instar larvae exposed to three concentrations of 2,4-D (0.1, 1.0, and 7.5 µg L-1). Larvae were collected after 24 and 96 h of exposure, and the expression of 42 genes, related to six subcellular mechanisms, was assessed by Real-Time PCR (RT-PCR). Besides, the activity of the enzymes catalase (CAT), glutathione S-transferase (GST), and acetylcholinesterase (AChE) was determined. The main metabolic route altered after exposure to 2,4-D was the endocrine system (mainly related to 20-hydroxyecdysone and juvenile hormone), confirming its endocrine disruptor potential. Four of the eleven stress response genes studied were down-regulated, and later exposure modulated DNA-repair genes suggesting genotoxic capacity. Moreover, only one gene from each detoxification phase was modulated at short exposure to 1.0 µg L-1. The molecular responses were not dose-dependent, and some early responses were not preserved after 96 h, indicating a transient response to the herbicide. Exposure to 2,4-D did not alter the activity of CAT, GST, and AChE enzymes. The responses described in this study reveal new mechanistic pathways of toxicity for 2,4-D in non-target organisms and highlight potential ecological consequences for chironomids in aquatic systems at the edges of agricultural fields.

Ecological Implications on Aquatic Food Webs Due to Effects of Pesticides on Invertebrate Predators in a Neotropical Region.

Predation presents specific behavioral characteristics for each species, and the interaction between prey and predator influences the structuring of the food web. Concerning insects, predation can be affected in different ways, such as exposure to chemical stressors, e.g., pesticides. Therefore, analyses were carried out of the effects of exposure to insecticide fipronil and the herbicide 2,4-D on predation, parameters of food selectivity, and the swimming behavior of two neotropical predatory aquatic insects of the families Belostomatidae (giant water bugs) and larvae of Libellulidae (dragonfly). These predatory insects were exposed for 24 h to a commercial formulation of the chlorophenoxy herbicide, 2,4-D at nominal concentrations of 200, 300, 700, and 1400 µg L-1, and to a commercial formulation of the phenylpyrazole insecticide, fipronil at nominal concentrations of 10, 70, 140, and 250 µg L-1. In a control treatment, the insects were placed in clean, unspiked water. At the end of the exposure, the maximum swimming speed of the predators was evaluated. Afterward, the predators were placed in clean water in a shared environment for 24 h with several prey species, including the cladoceran Ceriodaphnia silvestrii, larvae of the insect Chironomus sancticaroli, the amphipod Hyalella meinerti, the ostracod Strandesia trispinosa, and the oligochaete Allonais inaequalis for 24 h. After this period, the consumed prey was counted. The results reveal that predators from both families changed prey consumption compared with organisms from the control treatment, marked by a decrease after exposure to fipronil and an increase in consumption caused by 2,4-D. In addition, there were changes in the food preferences of both predators, especially when exposed to the insecticide. Exposure to fipronil decreased the swimming speed of Belostomatidae individuals, possibly due to its neurotoxic effect. Exposure to the insecticide and the herbicide altered prey intake by predators, which could negatively influence the complex prey-predator relationship and the functioning of aquatic ecosystems in contaminated areas.

The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.

The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.

Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood-brain barrier.

The migration of activated T cells across the blood-brain barrier (BBB) is a critical step in central nervous system (CNS) immune surveillance and inflammation. Whereas T cell diapedesis across the intact BBB seems to occur preferentially through the BBB cellular junctions, impaired BBB integrity during neuroinflammation is accompanied by increased transcellular T cell diapedesis. The underlying mechanisms directing T cells to paracellular versus transcellular sites of diapedesis across the BBB remain to be explored. By combining in vitro live-cell imaging of T cell migration across primary mouse brain microvascular endothelial cells (pMBMECs) under physiological flow with serial block-face scanning electron microscopy (SBF-SEM), we have identified BBB tricellular junctions as novel sites for T cell diapedesis across the BBB. Downregulated expression of tricellular junctional proteins or protein-based targeting of their interactions in pMBMEC monolayers correlated with enhanced transcellular T cell diapedesis, and abluminal presence of chemokines increased T cell diapedesis through tricellular junctions. Our observations assign an entirely novel role to BBB tricellular junctions in regulating T cell entry into the CNS. This article has an associated First Person interview with the first author of the paper.

Feasibility of Phosphoproteomics on Leftover Samples After RNA Extraction With Guanidinium Thiocyanate.

In daily practice, different types of biomolecules are usually extracted for large-scale "omics" analysis with tailored protocols. However, when sample material is limited, an all-in-one strategy is preferable. Although lysis of cells and tissues with urea is widely used for phosphoproteomic applications, DNA, RNA, and proteins can be simultaneously extracted from small samples using acid guanidinium thiocyanate-phenol-chloroform (AGPC). Use of AGPC for mass spectrometry-based phosphoproteomics was reported but has not yet been thoroughly evaluated against a classical phosphoproteomic protocol. Here we compared urea- with AGPC-based protein extraction, profiling phosphorylations in the DNA damage response pathway after ionizing irradiation of U2OS cells as proof of principle. On average we identified circa 9000 phosphosites per sample with both extraction methods. Moreover, we observed high similarity of phosphosite characteristics (e.g., 94% shared class 1 identifications) and deduced kinase activities (e.g., ATM, ATR, CHEK1/2, PRKDC). We furthermore extended our comparison to murine and human tissue samples yielding similar and highly correlated results for both extraction protocols. AGPC-based sample extraction can thus replace common cell lysates for phosphoproteomic workflows and may thus be an attractive way to obtain input material for multiple omics workflows, yielding several data types from a single sample.

Systematic review of reverse vaccinology and immunoinformatics data for non-viral sexually transmitted infections.

Sexually Transmitted Infections (STIs) are a public health burden rising in developed and developing nations. The World Health Organization estimates nearly 374 million new cases of curable STIs yearly. Global efforts to control their spread have been insufficient in fulfilling their objective. As there is no vaccine for many of these infections, these efforts are focused on education and condom distribution. The development of vaccines for STIs is vital for successfully halting their spread. The field of immunoinformatics is a powerful new tool for vaccine development, allowing for the identification of vaccine candidates within a bacterium's genome and allowing for the design of new genome-based vaccine peptides. The goal of this review was to evaluate the usage of immunoinformatics in research focused on non-viral STIs, identifying fields where research efforts are concentrated. Here we describe gaps in applying these techniques, as in the case of Treponema pallidum and Trichomonas vaginalis.

Phytotoxicity of 2,4-D and fipronil mixtures to three green manure species.

Sugarcane expansion has been associated with soil contamination by agrochemicals. Pesticides can affect plant growth, and their mixture might have potentiated effects on exposed species. This research aimed to evaluate the influence of fipronil on the phytotoxicity of 2,4-D on three green manure plant species: Canavalia ensiformis, Dolichos lablab, and Lupinus albus. Plants were exposed (for 21 days, at 25 °C) to a control soil and five concentrations of each pesticide and their combinations (36 treatments, considering a full-factorial approach). Effect concentrations of 50% growth inhibition (EC50) were estimated. No phytotoxicity effects were identified when plants were exposed to different fipronil concentrations (up to 0.12 mg kg-1). All species exposed to 2,4-D showed a decrease in shoot and root length and fresh/dry biomass. L. albus and D. lablab roots showed the highest sensitivity when exposed to 2,4-D among the endpoints (EC50 = 0.02 and 0.05 mg kg-1, respectively), while C. ensiformis roots were the most tolerant (EC50 = 0.98 mg kg-1). However, the interference of fipronil on the toxicity of 2,4-D was not detected in different mixture proportions, indicating no interaction between pesticides. Residues of 2,4-D might also impair other crops' growth, compromise productivity, and limit phytotechnologies for soil recovery.

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Cross-species transcriptomes reveal species-specific and shared molecular adaptations for plants development on iron-rich rocky outcrops soils.

BACKGROUND: Canga is the Brazilian term for the savanna-like vegetation harboring several endemic species on iron-rich rocky outcrops, usually considered for mining activities. Parkia platycephala Benth. and Stryphnodendron pulcherrimum (Willd.) Hochr. naturally occur in the cangas of Serra dos Carajás (eastern Amazonia, Brazil) and the surrounding forest, indicating high phenotypic plasticity. The morphological and physiological mechanisms of the plants' establishment in the canga environment are well studied, but the molecular adaptative responses are still unknown. To understand these adaptative responses, we aimed to identify molecular mechanisms that allow the establishment of these plants in the canga environment. RESULTS: Plants were grown in canga and forest substrates collected in the Carajás Mineral Province. RNA was extracted from pooled leaf tissue, and RNA-seq paired-end reads were assembled into representative transcriptomes for P. platycephala and S. pulcherrimum containing 31,728 and 31,311 primary transcripts, respectively. We identified both species-specific and core molecular responses in plants grown in the canga substrate using differential expression analyses. In the species-specific analysis, we identified 1,112 and 838 differentially expressed genes for P. platycephala and S. pulcherrimum, respectively. Enrichment analyses showed that unique biological processes and metabolic pathways were affected for each species. Comparative differential expression analysis was based on shared single-copy orthologs. The overall pattern of ortholog expression was species-specific. Even so, we identified almost 300 altered genes between plants in canga and forest substrates with conserved responses in the two species. The genes were functionally associated with the response to light stimulus and the circadian rhythm pathway. CONCLUSIONS: Plants possess species-specific adaptative responses to cope with the substrates. Our results also suggest that plants adapted to both canga and forest environments can adjust the circadian rhythm in a substrate-dependent manner. The circadian clock gene modulation might be a central mechanism regulating the plants' development in the canga substrate in the studied legume species. The mechanism may be shared as a common mechanism to abiotic stress compensation in other native species.

Beneficial effects of butyrate on brain functions: A view of epigenetic.

Brain functions are influenced by the presence, activity, and metabolism of the gut microbiota through the gut-microbiota-brain (GMB) axis. The consumption of a fiber-rich diet increases the content of short-chain fatty acids (SCFAs) from bacterial fermentation in the colon. Among SCFAs, butyrate stands out because of its wide array of biological functions, such as ability to influence brain functions. Pharmacologically, sodium butyrate (NaB) regulates gene expression in the brain, where it has several beneficial effects ranging from neurodegenerative diseases to behavioral disorders through inhibitors of histone deacetylases (HDACis). In this context, we review the mechanisms of action of the two types of butyrate on brain functions, with an emphasis on the epigenetic approach. Both types of butyrate are potentially interesting for the prevention and adjuvant therapy of neurological and psychological disorders due to their neuroprotective functions. However, further studies are needed to investigate the possible neuroepigenetic effects of butyrate derived from bacterial fermentation.

Respiratory Inductance Plethysmography to Assess Fatigability during Repetitive Work.

Cumulative fatigue during repetitive work is associated with occupational risk and productivity reduction. Usually, subjective measures or muscle activity are used for a cumulative evaluation; however, Industry 4.0 wearables allow overcoming the challenges observed in those methods. Thus, the aim of this study is to analyze alterations in respiratory inductance plethysmography (RIP) to measure the asynchrony between thorax and abdomen walls during repetitive work and its relationship with local fatigue. A total of 22 healthy participants (age: 27.0 ± 8.3 yrs; height: 1.72 ± 0.09 m; mass: 63.4 ± 12.9 kg) were recruited to perform a task that includes grabbing, moving, and placing a box in an upper and lower shelf. This task was repeated for 10 min in three trials with a fatigue protocol between them. Significant main effects were found from Baseline trial to the Fatigue trials (p < 0.001) for both RIP correlation and phase synchrony. Similar results were found for the activation amplitude of agonist muscle (p < 0.001), and to the muscle acting mainly as a joint stabilizer (p < 0.001). The latter showed a significant effect in predicting both RIP correlation and phase synchronization. Both RIP correlation and phase synchronization can be used for an overall fatigue assessment during repetitive work.

The Role of Axonal Transport in Glaucoma.

Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs) and leads to progressive vision loss. The first pathological signs can be seen at the optic nerve head (ONH), the structure where RGC axons leave the retina to compose the optic nerve. Besides damage of the axonal cytoskeleton, axonal transport deficits at the ONH have been described as an important feature of glaucoma. Axonal transport is essential for proper neuronal function, including transport of organelles, synaptic components, vesicles, and neurotrophic factors. Impairment of axonal transport has been related to several neurodegenerative conditions. Studies on axonal transport in glaucoma include analysis in different animal models and in humans, and indicate that its failure happens mainly in the ONH and early in disease progression, preceding axonal and somal degeneration. Thus, a better understanding of the role of axonal transport in glaucoma is not only pivotal to decipher disease mechanisms but could also enable early therapies that might prevent irreversible neuronal damage at an early time point. In this review we present the current evidence of axonal transport impairment in glaucomatous neurodegeneration and summarize the methods employed to evaluate transport in this disease.

Different loci control resistance to different isolates of the same race of Colletotrichum lindemuthianum in common bean.

KEY MESSAGE: Linkage and genome-wide association analyses using high-throughput SNP genotyping revealed different loci controlling resistance to different isolates of race 65 of Colletotrichum lindemuthianum in common bean. Development of varieties with durable resistance to anthracnose is a major challenge in common bean breeding programs because of the extensive virulence diversity of Colletotrichum lindemuthianum fungus. We used linkage and genome-wide association analyses to tap the genomic regions associated with resistance to different isolates of race 65. Linkage mapping was done using an F2 population derived from the cross between the Mesoamerican common beans BRS Estilo x Ouro Vermelho, inoculated with two different isolates of race 65. Association genetics relied on a diversity common bean panel containing 189 common bean accessions inoculated with five different isolates of race 65 as an attempt to validate the linkage analysis findings and, eventually, identify other genomic regions associated with resistance to race 65. The F2 population and diversity panel were genotyped with the BARCBean6K_3 Illumina BeadChip containing 5398 SNP markers. Both linkage and genome-wide association analyses identified different loci controlling resistance to different isolates of race 65 on linkage group Pv04. Genome-wide association analysis also detected loci on Pv05, Pv10 and Pv11 associated with resistance to race 65. These findings indicate that resistance to race 65 can be overcome by the virulence diversity among different isolates of the same race and could lead to the loss of resistance after cultivar release. We identified 25 resistant common bean cultivars to all five isolates of race 65 in the diversity panel. The accessions should be useful to develop cultivars combining different resistance genes that favor durable resistance to anthracnose in common bean.

Cerebral venous thrombosis and severe acute respiratory syndrome coronavirus-2 infection: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection predisposes patients to arterial and venous thrombosis. This study aimed to systematically review the available evidence in the literature for cerebral venous thrombosis (CVT) in association with coronavirus disease-2019 (COVID-19). METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases to identify cases of COVID-19-associated CVT. The search period spanned 1 January 2020 to 1 December 2020, and the review protocol (PROSPERO-CRD42020214327) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Identified studies were evaluated for bias using the Newcastle-Ottawa scale. A proportion meta-analysis was performed to estimate the frequency of CVT among hospitalized COVID-19 patients. RESULTS: We identified 57 cases from 28 reports. Study quality was mostly classified as low. CVT symptoms developed after respiratory disease in 90%, and the mean interval was 13 days. CVT involved multiple sites in 67% of individuals, the deep venous system was affected in 37%, and parenchymal hemorrhage was found in 42%. Predisposing factors for CVT beyond SARS-CoV-2 infection were present in 31%. In-hospital mortality was 40%. Using data from 34,331 patients, the estimated frequency of CVT among patients hospitalized for SARS-CoV-2 infection was 0.08% (95% confidence interval [CI]: 0.01-0.5). In an inpatient setting, CVT accounted for 4.2% of cerebrovascular disorders in individuals with COVID-19 (cohort of 406 patients, 95% CI: 1.47-11.39). CONCLUSIONS: Cerebral venous thrombosis in the context of SARS-CoV-2 infection is a rare, although there seems to be an increased relative risk. High suspicion is necessary, because the diagnosis of this potentially life-threatening condition in COVID-19 patients can be challenging. Evidence is still scarce on the pathophysiology and potential prevention of COVID-19-associated CVT.

Association Among Preoperative Cognitive Performance, Regional Cerebral Oxygen Saturation, and Postoperative Delirium in Older Portuguese Patients.

BACKGROUND: Postoperative delirium is common among older patients and preoperative identification of high-risk patients is widely recommended. The aim of this study was to assess whether preoperative cognitive performance using brief screening tools or regional cerebral oxygen saturation (Scto2) was associated with the development of postoperative delirium in older Portuguese patients undergoing elective surgery. METHODS: Prospective observational cohort study where preoperative cognitive screening tools (Mini-Cog, Mini-Mental State Examination, verbal fluency) and Scto2 (INVOS 5100C; Medtronic, Ireland) were assessed in 238 patients ≥65 years old undergoing elective surgery between July 2017 and May 2019 at a tertiary academic center in Portugal. The primary outcome was postoperative delirium detected by the 3D-Confusion Assessment Method. Data were analyzed by univariate analysis and multivariable logistic regression. RESULTS: Delirium was identified in 53 patients (22%); 162 patients (68%) had completed only 4 years of education. On multivariable analysis, probable cognitive impairment tested by the Mini-Cog (odds ratio [OR] = 1.57; 95% confidence interval [CI], 0.70-3.53; corrected P value >.999), by the Mini-Mental State Examination (OR = 2.75; 95% CI, 1.23-6.13; corrected P value = .052), and by the animal verbal fluency test (OR = 1.24; 95% CI, 0.49-3.16; corrected P value >.999) were not significantly associated with the development of postoperative delirium. In contrast, lower preoperative Scto2 (OR = 1.08; 95% CI, 1.02-1.14; corrected P value = .024 for each point decrease in Scto2) was associated with postoperative delirium. CONCLUSIONS: We did not find enough evidence to suggest that poor preoperative cognitive performance was significantly associated with the development of postoperative delirium in an older Portuguese surgical population with an overall low level of formal education, but rather that preoperative Scto2 may be helpful in identifying patients at risk for delirium.

Mean Platelet Volume is a Prognostic Marker in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

BACKGROUND AND OBJECTIVES: There is conflicting data regarding the association between platelet parameters and prognosis of stroke patients treated with intravenous thrombolysis. We aimed to analyze this association in a cohort of patients treated with rtPA. MATERIAL AND METHODS: Retrospective, observational study in adult ischemic stroke patients treated with rtPA between January 2015 and February 2017. Demographic and clinical characteristics, stroke severity (NIHSS), etiology (TOAST), mean platelet volume (MPV), platelet count (PC), platelet distribution width (PDW) and functional outcome (mRS) at discharge and 90 days were recorded. The association between platelet parameters and unfavorable prognosis (mRS 3-6) was tested using non-parametric tests and logistic regression analysis. RESULTS: 267 patients were included, 134 (50.2%) females, with a median (IQR) age of 74 years (64-82). The median admission NIHSS was 14 (8-19) and the most frequent etiology was cardioembolism (n = 115, 43.1%). At discharge, 170 (63.7%) patients had mRS 3-6. MPV values were higher in patients with mRS 3-6 (median 8.2fL versus 7.8fL, p = 0.013). This association remained significant (OR = 1.36, 95% CI 1.003-1.832, p = 0.048) after adjustment for variables associated with prognosis. There were no significant associations between other platelet parameters and prognosis. There was a trend to unfavorable prognosis at 90 days in patients with higher MPV. Regarding the association between platelet parameters and hemorrhagic transformation, higher PDW was associated with more severe hemorrhagic transformation (PH1/PH2). CONCLUSIONS: Higher MPV values were associated with unfavorable prognosis at discharge in patients treated with intravenous thrombolysis. Future studies should address its added value in stroke prediction models.

Direct acidification of requeijão cremoso model by lactobionic acid: physical, chemical and antimicrobial effects.

ABSTRACT: Lactobionic acid (LBA) shows singular properties (antioxidant and antimicrobial). However, few studies aim to test them in foods and confirm the actual occurrence of properties. The present study aims to apply LBA/lactic acid in the production of requeijão cremoso model in order to recognize some of the effects caused by the component as a food additive. The effects on the requeijão cremoso model were evaluated by the final properties of the product: water activity, rheological properties, antioxidant and antimicrobial capacity. Model of requeijão completely acidified with LBA showed the maximum antioxidant activity (88%). The results revealed a potential of application of LBA for microbial inhibition. All model produced presented pseudo plastic behaviour.

Early Recanalization in Patients With Cerebral Venous Thrombosis Treated With Anticoagulation.

Background and Purpose- The hypothesis that venous recanalization prevents progression of venous infarction is not established in patients with cerebral venous thrombosis (CVT). Evidence is also scarce on the association between residual symptoms, particularly headache, and the recanalization grade. We aimed to assess, in patients with CVT treated with standard anticoagulation, (1) the rate of early venous recanalization, (2) whether lack of early recanalization was predictor of parenchymal brain lesion progression, and (3) the prevalence and features of persistent headache according to the recanalization grade achieved. Methods- PRIORITy-CVT (Pathophysiology of Venous Infarction - Prediction of Infarction and Recanalization in CVT) was a multicenter, prospective, cohort study including patients with newly diagnosed CVT. Standardized magnetic resonance imaging was performed at inclusion (≤24 hours of therapeutic anticoagulation), days 8 and 90. Potential imaging predictors of recanalization were predefined and analyzed at each anatomical segment. Primary outcomes were rate of early recanalization and brain lesion progression at day 8. Secondary outcomes were headache (days 8 and 90) and functional outcome (modified Rankin Scale at days 8 and 90). Results- Sixty eight patients with CVT were included, of whom 30 (44%) had parenchymal lesions. At the early follow-up (n=63; 8±2 days), 68% (n=43) of patients had partial recanalization and 6% (n=4) full recanalization. Early recanalization was associated both with early regression (P=0.03) and lower risk of enlargement of nonhemorrhagic lesions (P=0.02). Lesions showing diffusion restriction (n=12) were fully reversible in 66% of cases, particularly in patients showing early venous recanalization. Evidence of new or enlarged hemorrhagic lesions, headache at days 8 and 90, and unfavorable functional outcome at days 8 and 90 were not significantly different in patients achieving recanalization. Conclusions- Venous recanalization started within the first 8 days of therapeutic anticoagulation in most patients with CVT and was associated with early regression of nonhemorrhagic lesions, including venous infarction. There was an association between persistent venous occlusion at day 8 and enlargement of nonhemorrhagic lesions.