Effect of zamicastat on blood pressure and heart rate response to cold pressor test: A double-blind, randomized, placebo-controlled study in healthy subjects.

AIMS: Dopamine beta-hydroxylase (DßH) inhibitors, like zamicastat, hold promise for treating pulmonary arterial hypertension. This study aimed to validate the mechanism of action of zamicastat by studying its effect on the overdrive of the sympathetic nervous system (SNS). METHODS: A single-centre, prospective, double-blind, randomized, placebo-controlled, crossover study evaluated the effect of 400 mg zamicastat in 22 healthy male subjects. Cold pressor test (CPT) was performed at screening and each treatment period on Days -1 and 10. Plasma and 24 h-urine levels of dopamine (DA), epinephrine (EPI) and norepinephrine (NE), and plasma DßH activity, were measured. RESULTS: Compared to placebo, zamicastat showed a - 4.62 mmHg decrease in systolic blood pressure during the cold stimulus vs. rest phases on Day 10 of CPT (P = .020). Zamicastat decreased mean arterial pressure response to cold stimulus during CPT (-2.62 mmHg; P = .025). At Day 10, zamicastat significantly increased plasma DA, before CPT (12.63 ng/L; P = .040) and after CPT (19.22 ng/L; P = .001) as well as the estimated plasma EPI change from baseline after CPT (P = .040). Inhibition of plasma DßH activity ranged from 19.8% to 25.0%. At Day 10, significant reductions in 24-h urinary excretion of EPI (P = .002) and NE (P = .001) were observed. Zamicastat Cτ geometric mean ± GSD ranged from 45.86 ± 1.46 ng/mL on Day 3 to 58.64 ± 1.52 ng/mL on Day 10, with moderate inter-individual variability (CV: 32.6%-36.6%). Steady state was already achieved on Day 6. CONCLUSIONS: Our results demonstrated the effect of zamicastat on the overdrive sympathetic response to cold stimulus, confirming its potential as SNS modulator.

Towards a Modular On-Premise Approach for Data Sharing.

The growing demand for everyday data insights drives the pursuit of more sophisticated infrastructures and artificial intelligence algorithms. When combined with the growing number of interconnected devices, this originates concerns about scalability and privacy. The main problem is that devices can detect the environment and generate large volumes of possibly identifiable data. Public cloud-based technologies have been proposed as a solution, due to their high availability and low entry costs. However, there are growing concerns regarding data privacy, especially with the introduction of the new General Data Protection Regulation, due to the inherent lack of control caused by using off-premise computational resources on which public cloud belongs. Users have no control over the data uploaded to such services as the cloud, which increases the uncontrolled distribution of information to third parties. This work aims to provide a modular approach that uses cloud-of-clouds to store persistent data and reduce upfront costs while allowing information to remain private and under users' control. In addition to storage, this work also extends focus on usability modules that enable data sharing. Any user can securely share and analyze/compute the uploaded data using private computing without revealing private data. This private computation can be training machine learning (ML) models. To achieve this, we use a combination of state-of-the-art technologies, such as MultiParty Computation (MPC) and K-anonymization to produce a complete system with intrinsic privacy properties.

Provisioning, Authentication and Secure Communications for IoT Devices on FIWARE.

The increasing pervasiveness of the Internet of Things is resulting in a steady increase of cyberattacks in all of its facets. One of the most predominant attack vectors is related to its identity management, as it grants the ability to impersonate and circumvent current trust mechanisms. Given that identity is paramount to every security mechanism, such as authentication and access control, any vulnerable identity management mechanism undermines any attempt to build secure systems. While digital certificates are one of the most prevalent ways to establish identity and perform authentication, their provision at scale remains open. This provisioning process is usually an arduous task that encompasses device configuration, including identity and key provisioning. Human configuration errors are often the source of many security and privacy issues, so this task should be semi-autonomous to minimize erroneous configurations during this process. In this paper, we propose an identity management (IdM) and authentication method called YubiAuthIoT. The overall provisioning has an average runtime of 1137.8 ms ±65.11+δ. We integrate this method with the FIWARE platform, as a way to provision and authenticate IoT devices.

Micro-bead injection spectroscopy for label-free automated determination of immunoglobulin G in human serum.

Immunoglobulin G (IgG) represents the major fraction of antibodies in healthy adult human serum, and deviations from physiological levels are a generic marker of disease corresponding to different pathologies. Therefore, screening methods for IgG evaluation are a valuable aid to diagnostics. The present work proposes a rapid, automatic, and miniaturized method based on UV-vis micro-bead injection spectroscopy (µ-BIS) for the real-time determination of human serum IgG with label-free detection. Relying on attachment of IgG in rec-protein G immobilized in Sepharose 4B, a bioaffinity column is automatically assembled, where IgG is selectively retained and determined by on-column optical density measurement. A "dilution-and-shoot" approach (50 to 200 times) was implemented without further sample treatment because interferences were flushed out of the column upon sample loading, with minimization of carryover and cross-contamination by automatically discarding the sorbent (0.2 mg) after each determination. No interference from human serum albumin at 60 mg mL-1 in undiluted sample was found. The method allowed IgG determination in the range 100-300 µg mL-1 (corresponding to 5.0-60 mg mL-1 in undiluted samples), with a detection limit of 33 µg mL-1 (1.7 mg mL-1 for samples, dilution factor of 50). RSD values were < 9.4 and < 11.7%, for intra and inter-assay precision, respectively, while recovery values for human serum spiked with IgG at high pathological levels were 97.8-101.4%. Comparison to commercial ELISA kit showed no significant difference for tested samples (n = 8). Moreover, time-to-result decreased from several hours to < 5 min and analysis cost decreased 10 times, showing the potential of the proposed approach as a point-of-care method. Graphical abstract Micro-Bead Injection Spectroscopy method for real time, automated and label-free determination of total serum human Immunoglobulin G (IgG). The method was designed for Lab-on-Valve (LOV) platforms using a miniaturised protein G bioaffinity separative approach. IgG are separated from serum matrix components upon quantification with low non-specific binding in less than 5 min.

Highlights from the Ninth International Symposium of Thrombosis and Anticoagulation (ISTA IX), October 15, 2016, Salvador, Bahia, Brazil.

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Ninth International Symposium of Thrombosis and Anticoagulation was held in Salvador, Bahia, Brazil, on October 15, 2016. This scientific program was developed by clinicians for clinicians and was promoted by two major clinical research institutes-the Brazilian Clinical Research Institute and the Duke Clinical Research Institute of the Duke University School of Medicine. Comprising academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

In vitro embryos production after oocytes treatment with forskolin.

The inhibition of nuclear maturation allows time for the oocyte to accumulate molecules that are important for embryonic development. Thus, the objective of this work was to evaluate the effect of blocking oocyte meiosis with the addition of forskolin, an efficient inhibitor of nuclear maturation, in in vitro maturation (IVM) medium. Forskolin was added to the IVM medium for 6 h at concentrations of 0.1 mM, 0.05 mM or 0.025 mM, then the oocytes were allowed to mature in drug-free medium for 18 h. The oocytes were assessed for the stage of nuclear maturation, the activity and distribution of mitochondria, oocyte ultrastructure, the number of viable cells and the apoptosis rate. After forskolin treatment, the oocytes were fertilized in vitro and cultured for 7 days. On day 7, the blastocyst rate, the ultrastructure, the number of intact cells and the apoptosis rate of the blastocysts were measured. No differences were observed for the stage of nuclear maturation of the oocyte, the mitochondrial activity and distribution, the blastocyst rate or total number of intact cells. However, a higher rate of apoptosis was observed in the blastocysts produced from oocytes blocked for 6 h with the higher concentration of forskolin (P < 0.05). We conclude that all the experimental groups reached the MII stage after the addition of forskolin and that the highest concentration of forskolin caused cellular degeneration without harming embryo production on the 7th day.

DNA damage in blood cells exposed to low-level lasers.

BACKGROUND AND OBJECTIVE: In regenerative medicine, there are increasing applications of low-level lasers in therapeutic protocols for treatment of diseases in soft and in bone tissues. However, there are doubts about effects on DNA, and an adequate dosimetry could improve the safety of clinical applications of these lasers. This work aimed to evaluate DNA damage in peripheral blood cells of Wistar rats induced by low-level red and infrared lasers at different fluences, powers, and emission modes according to therapeutic protocols. MATERIAL AND METHODS: Peripheral blood samples were exposed to lasers and DNA damage was accessed by comet assay. In other experiments, DNA damage was accessed in blood cells by modified comet assay using formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III enzymes. RESULTS: Data show that exposure to low-level red and infrared lasers induce DNA damage depending on fluence, power and emission mode, which are targeted by Fpg and endonuclease III. CONCLUSION: Oxidative DNA damage should be considered for therapeutic efficacy and patient safety in clinical applications based on low-level red and infrared lasers.

Crucial surviving aspects for vitrified in vitro-produced bovine embryos.

The objective of the present study was to correlate some parameters (cleavage, blastocyst production, quality degree score, total cell number, fresh apoptosis and lipid content) with embryo survival after cryopreservation. A total of 1727 in vitro-produced bovine blastocysts were used to establish the parameters (mean ± standard error of the mean (SEM)) for cleavage (85.6 ± 0.8), blastocyst production (39.9 ± 1.4), quality degree score (1.6 ± 0.1), total cell number (140.1 ± 2.9), fresh apoptosis (20.8 ± 1.1) and lipid content (21.3 ± 0.8 droplets). On the same way 1316 blastocysts were vitrified for the determination of post-cryopreservation embryo survival (49.4 ± 1.9). Fresh apoptosis rate and total lipid droplets value were correlated (P < 0.05) with embryo survival after cryopreservation (r = 0.91 and r = 0.59; respectively). However, cleavage, blastocyst production, quality degree score and total cell number were not correlated (P > 0.05) with embryo cryotolerance (r = 0.23, r = 0.38, r = 0.22 and r = 0.28; respectively). Therefore, the increased lipid content was moderately correlated with apoptosis in vitrified blastocysts. On the other hand, increased apoptosis in fresh blastocysts was strongly correlated with apoptosis in vitrified blastocysts, which indicated that the apoptosis rate in fresh embryos was a better parameter than the lipid content to predict post-vitrification embryo survival.

Forskolin effect on the cryosurvival of in vitro-produced bovine embryos in the presence or absence of fetal calf serum.

The objective of this study was to assess the viability and cryotolerance of zebu embryos produced in vitro with or without the addition of fetal calf serum (FCS) and forskolin (F). Embryos produced in vivo were used as a control. Presumptive zygotes were cultured in modified synthetic oviductal fluid supplemented with amino acids (SOFaa), bovine serum albumin (BSA) and with (2.5%) or without (0%) FCS. On day 6 of growth, the embryos from each group were divided into treatments with or without 10 µM F to induce embryonic lipolysis, comprising a total of four experimental groups: 2.5% FCS, 0% FCS, 2.5% + F and 0% + F. For vitrification, embryos were exposed to vitrification solution 1 (5 M EG (ethylene glycol)) for 3 min and then transferred to vitrification solution 2 (7 M EG, 0.5 M galactose solution and 18% (w/v) Ficoll 70) before being introduced to liquid nitrogen. The presence of FCS in the culture medium resulted in the production of embryos with a similar rate of damaged cells compared with in vivo-produced embryos. After vitrification, the 2.5% FCS group had a significantly higher rate of damaged cells when compared with the other groups (P < 0.05). The results of this experiment indicated that the omission of FCS and the addition of forskolin do not have deleterious effect on embryo production rates. In addition, embryos produced in the presence of FCS had greater sensitivity to cryopreservation, but this effect was reversed when forskolin was added to the medium, which improved embryo survival without affecting embryo development and quality after vitrification.

Insights on antioxidant assays for biological samples based on the reduction of copper complexes-the importance of analytical conditions.

Total antioxidant capacity assays are recognized as instrumental to establish antioxidant status of biological samples, however the varying experimental conditions result in conclusions that may not be transposable to other settings. After selection of the complexing agent, reagent addition order, buffer type and concentration, copper reducing assays were adapted to a high-throughput scheme and validated using model biological antioxidant compounds of ascorbic acid, Trolox (a soluble analogue of vitamin E), uric acid and glutathione. A critical comparison was made based on real samples including NIST-909c human serum certified sample, and five study samples. The validated method provided linear range up to 100 µM Trolox, (limit of detection 2.3 µM; limit of quantification 7.7 µM) with recovery results above 85% and precision <5%. The validated developed method with an increased sensitivity is a sound choice for assessment of TAC in serum samples.

Calibration system correction factor for measuring the reference air kerma rate (RAKR) applied to high dose rate192Ir sources (HDR).

The aim of this study was to use computer simulation to analyze the impact of the aluminum fixing support on the Reference Air Kerma (RAK), a physical quantity obtained in a calibration system that was experimentally developed in the Laboratory of Radiological Sciences of the University of the State of Rio de Janeiro (LCR-UERJ). Correction factors due to scattered radiation and the geometry of the192Ir sources were also sought to be determined. The computational simulation was validated by comparing some parameters of the experimental results with the computational results. These parameters were: verification of the inverse square law of distance, determination of (RAKR), analysis of the source spectrum with and without encapsulation, and the sensitivity curve of the Sourcecheck 4PI ionization chamber response, as a function of the distance from the source along the axial axis, using the microSelectron-v2 (mSv2) and GammaMedplus (GMp) sources. Kerma was determined by activity in the Reference air, with calculated values of 1.725 × 10-3U. Bq-1and 1.710 × 10-3U. Bq-1for the ionization chamber NE 2571 and TN 30001, respectively. The expanded uncertainty for these values was 0.932% and 0.919%, respectively, for a coverage factor (k = 2). The correction factor due to the influence of the aluminum fixing support for measurements at 1 cm and 10 cm from the source was 0.978 and 0.969, respectively. The geometric correction factor of the sources was ksg= 1.005 with an expanded uncertainty of 0.7% for a coverage factor (k = 2). This value has a difference of approximately 0.2% compared to the experimental values.

Efficacy, safety, and tolerability of adjunctive eslicarbazepine acetate in patients with focal to bilateral tonic-clonic seizures.

OBJECTIVE: To report the efficacy, safety, and tolerability of adjunctive eslicarbazepine acetate (ESL) treatment in reducing focal to bilateral tonic-clonic seizures (FBTCS). METHODS: Data were pooled from 3 randomized clinical trials (RCTs) of adjunctive ESL in patients with focal seizures. Patients treated with 800 or 1200 mg/day ESL and who experienced ≥ 1 FBTCS during baseline were included. Efficacy was measured using FBTCS standardized seizure frequency (SSF), responder rates (≥50%, ≥75%, and 100%), and time to first FBTCS. Adverse events (AEs) were tabulated for each subgroup. RESULTS: Of the original 1447 patients, 438 patients in the safety population were included with ≥ 1 FBTCS at baseline (efficacy population, n = 429). Patients with ≥ 2 FBTCS (safety, n = 354; efficacy, n = 346) and ≥ 3 FBTCS (safety, n = 294; efficacy, n = 288) at baseline were also analyzed. The 1200 mg/day ESL group experienced lower least squares mean SSF vs placebo in patients with ≥ 1 baseline FBTCS (P = 0.0395) and ≥ 3 baseline FBTCS (P = 0.0091). The 50% responder rates improved for 1200 mg/day ESL vs placebo (≥1 FBTCS, P = 0.005; ≥2 FBTCS, P = 0.0063; ≥3 FBTCS, P = 0.0016). The 75% responder rates improved with 1200 mg/day ESL vs placebo (≥1 FBTCS, P = 0.0315; ≥2 FBTCS, P = 0.0215; ≥3 FBTCS, P = 0.0099), and with 800 mg/day ESL for ≥ 2 FBTCS at baseline (P = 0.0486). The 100% responder rate was higher in patients treated with 1200 mg/day ESL (not significant). Time to first FBTCS was longer with both 800 (P = 0.0008) and 1200 mg/day (P = 0.0020) ESL vs placebo for the ≥ 1 FBTCS subgroup, and with 1200 mg/day ESL for ≥ 2 FBTCS (P = 0.0060) and ≥ 3 FBTCS (P = 0.0152) subgroups. Overall, AEs occurred at similar rates across subgroups, and were lower than the original RCTs. CONCLUSION: Adjunctive ESL produced a robust response in patients with FBTCS, a seizure type associated with SUDEP and high injury rates. Adjunctive ESL was well tolerated in patients who experienced FBTCS.

Drug-Drug Interaction between Oral Zamicastat and Continuous Epoprostenol Infusion at Steady-State Conditions in Healthy Subjects.

This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single-center, open-label, two-period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8-day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat-to-epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for Cav,ss and area under the plasma concentration-time curve from time 0 up to 16 h at steady state (AUC0-16,ss) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%-125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC0-τ,ss, the zamicastat plus epoprostenol-to-zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat Cmax,ss, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, Cmax,ss and AUC0-τ,ss and the zamicastat plus epoprostenol-to-zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for Cmax,ss and between 21% and 41% for AUC0-τ,ss, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant.

Microcarrier-based fluorescent yeast estrogen screen assay for fast determination of endocrine disrupting compounds.

The presence of endocrine-disrupting compounds (EDCs) in water poses a significant threat to human and animal health, as recognized by regulatory agencies throughout the world. The Yeast Estrogen Screen (YES) assay is an excellent method to evaluate the presence of these compounds in water due to its simplicity and capacity to assess the bioaccessible forms/fractions of these compounds. In the presence of a compound with estrogenic activity, Saccharomyces cerevisiae cells, containing a lacZ reporter gene encoding the enzyme ß-galactosidase, are induced, the enzyme is synthesised, and released to the extracellular medium. In this work, a YES-based approach encompassing the use of a lacZ reporter gene modified strain of S. cerevisiae, microcarriers as solid support, and a fluorescent substrate, fluorescein di-ß-d-galactopyranoside, is proposed, allowing for the assessment of EDCs' presence after only 2 h of incubation. The proposed method provided an EC50 of 0.17 ± 0.03 nM and an LLOQ of 0.03 nM, expressed as 17ß-estradiol. The assessment of different EDCs provided EC50 values between 0.16 and 1.2 × 103 nM. After application to wastewaters, similar results were obtained for EDCs screening, much faster, compared to the conventional 45 h spectrophotometric procedure using a commercial kit, showing potential for onsite high-throughput screening of environmental contamination.

Automated microdialysis-based system for in situ microsampling and investigation of lead bioavailability in terrestrial environments under physiologically based extraction conditions.

In situ automatic microdialysis sampling under batch-flow conditions is herein proposed for the first time for expedient assessment of the kinetics of lead bioaccessibility/bioavailability in contaminated and agricultural soils exploiting the harmonized physiologically based extraction test (UBM). Capitalized upon a concentric microdialysis probe immersed in synthetic gut fluids, the miniaturized flow system is harnessed for continuous monitoring of lead transfer across the permselective microdialysis membrane to mimic the diffusive transport of metal species through the epithelium of the stomach and of the small intestine. Besides, the addition of the UBM gastrointestinal fluid surrogates at a specified time frame is fully mechanized. Distinct microdialysis probe configurations and membranes types were investigated in detail to ensure passive sampling under steady-state dialytic conditions for lead. Using a 3-cm-long polysulfone membrane with averaged molecular weight cutoff of 30 kDa in a concentric probe and a perfusate flow rate of 2.0 µL min(-1), microdialysis relative recoveries in the gastric phase were close to 100%, thereby omitting the need for probe calibration. The automatic leaching method was validated in terms of bias in the analysis of four soils with different physicochemical properties and containing a wide range of lead content (16 ± 3 to 1216 ± 42 mg kg(-1)) using mass balance assessment as a quality control tool. No significant differences between the mass balance and the total lead concentration in the suite of analyzed soils were encountered (α = 0.05). Our finding that the extraction of soil-borne lead for merely one hour in the GI phase suffices for assessment of the bioavailable fraction as a result of the fast immobilization of lead species at near-neutral conditions would assist in providing risk assessment data from the UBM test on a short notice.

An Innovative Faster R-CNN-Based Framework for Breast Cancer Detection in MRI.

Replacing lung cancer as the most commonly diagnosed cancer globally, breast cancer (BC) today accounts for 1 in 8 cancer diagnoses and a total of 2.3 million new cases in both sexes combined. An estimated 685,000 women died from BC in 2020, corresponding to 16% or 1 in every 6 cancer deaths in women. BC represents a quarter of a total of cancer cases in females and by far the most commonly diagnosed cancer in women in 2020. However, when detected in the early stages of the disease, treatment methods have proven to be very effective in increasing life expectancy and, in many cases, patients fully recover. Several medical imaging modalities, such as X-rays Mammography (MG), Ultrasound (US), Computer Tomography (CT), Magnetic Resonance Imaging (MRI), and Digital Tomosynthesis (DT) have been explored to support radiologists/physicians in clinical decision-making workflows for the detection and diagnosis of BC. In this work, we propose a novel Faster R-CNN-based framework to automate the detection of BC pathological Lesions in MRI. As a main contribution, we have developed and experimentally (statistically) validated an innovative method improving the "breast MRI preprocessing phase" to select the patient's slices (images) and associated bounding boxes representing pathological lesions. In this way, it is possible to create a more robust training (benchmarking) dataset to feed Deep Learning (DL) models, reducing the computation time and the dimension of the dataset, and more importantly, to identify with high accuracy the specific regions (bounding boxes) for each of the patient's images, in which a possible pathological lesion (tumor) has been identified. As a result, in an experimental setting using a fully annotated dataset (released to the public domain) comprising a total of 922 MRI-based BC patient cases, we have achieved, as the most accurate trained model, an accuracy rate of 97.83%, and subsequently, applying a ten-fold cross-validation method, a mean accuracy on the trained models of 94.46% and an associated standard deviation of 2.43%.

Acute kidney injury in coronavirus infectious disease: a study of incidence, risk factors, and prognosis during the first wave of the disease in Brazil.

INTRODUCTION: Acute kidney injury (AKI) is one of the main complications of COVID-19 caused by SARS-CoV-2. This study aimed to evaluate the incidence of AKI in Brazilian hospitalized patients diagnosed with COVID-19 and identify the risk factors associated with its onset and those associated with its prognosis. METHODS: A prospective cohort study of hospitalized patients diagnosed with COVID-19 at a public and tertiary university hospital in São Paulo from March to December 2020. RESULTS: There were 347 patients hospitalized with COVID-19, 52.4% were admitted to the intensive care unit (ICU) and 47.6% were admitted to the wards. The overall incidence of AKI was 46.4%, more frequent in the ICU (68.1% vs 22.4, p < 0.01) and the overall mortality was 36.1%. Acute kidney replacement therapy was indicated in 46.6% of patients with AKI. In the general population, the factors associated with AKI were older age (OR 1.03, CI 1-1.05, p < 0.05), mechanical ventilation (OR 1.23, CI 1.06-1.83, p < 0.05), presence of proteinuria (OR 1.46, CI 1.22-1.93, p < 0.05), and use of vasoactive drugs (OR 1.26, CI 1.07-1.92, p < 0.05). Mortality was higher in the elderly (OR 1.08, CI 1.04-1.11, p < 0.05), in those with AKI (OR 1.12, CI 1.02-2.05, p < 0.05), particularly KDIGO stage 3 AKI (OR 1.10, CI 1.22-2.05, p < 0.05) and in need of mechanical ventilation (OR 1.13, CI 1.03-1.60, p < 0.05). CONCLUSION: AKI was frequent in hospitalized patients with COVID-19 and the factors associated with its development were older age, mechanical ventilation, use of vasoactive drugs, and presence of proteinuria, being a risk factor for death.

Empowering Deaf-Hearing Communication: Exploring Synergies between Predictive and Generative AI-Based Strategies towards (Portuguese) Sign Language Interpretation.

Communication between Deaf and hearing individuals remains a persistent challenge requiring attention to foster inclusivity. Despite notable efforts in the development of digital solutions for sign language recognition (SLR), several issues persist, such as cross-platform interoperability and strategies for tokenizing signs to enable continuous conversations and coherent sentence construction. To address such issues, this paper proposes a non-invasive Portuguese Sign Language (Língua Gestual Portuguesa or LGP) interpretation system-as-a-service, leveraging skeletal posture sequence inference powered by long-short term memory (LSTM) architectures. To address the scarcity of examples during machine learning (ML) model training, dataset augmentation strategies are explored. Additionally, a buffer-based interaction technique is introduced to facilitate LGP terms tokenization. This technique provides real-time feedback to users, allowing them to gauge the time remaining to complete a sign, which aids in the construction of grammatically coherent sentences based on inferred terms/words. To support human-like conditioning rules for interpretation, a large language model (LLM) service is integrated. Experiments reveal that LSTM-based neural networks, trained with 50 LGP terms and subjected to data augmentation, achieved accuracy levels ranging from 80% to 95.6%. Users unanimously reported a high level of intuition when using the buffer-based interaction strategy for terms/words tokenization. Furthermore, tests with an LLM-specifically ChatGPT-demonstrated promising semantic correlation rates in generated sentences, comparable to expected sentences.

Antiepileptogenesis after stroke-trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate.

There is currently no evidence to support the use of antiseizure medications to prevent unprovoked seizures following stroke. Experimental animal models suggested a potential antiepileptogenic effect for eslicarbazepine acetate (ESL), and a Phase II, multicenter, randomized, double-blind, placebo-controlled study was designed to test this hypothesis and assess whether ESL treatment for 1 month can prevent unprovoked seizures following stroke. We outline the design and status of this antiepileptogenesis study, and discuss the challenges encountered in its execution to date. Patients at high risk of developing unprovoked seizures after acute intracerebral hemorrhage or acute ischemic stroke were randomized to receive ESL 800 mg/d or placebo, initiated within 120 hours after primary stroke occurrence. Treatment continued until Day 30, then tapered off. Patients could receive all necessary therapies for stroke treatment according to clinical practice guidelines and standard of care, and are being followed up for 18 months. The primary efficacy endpoint is the occurrence of a first unprovoked seizure within 6 months after randomization ("failure rate"). Secondary efficacy assessments include the occurrence of a first unprovoked seizure during 12 months after randomization and during the entire study; functional outcomes (Barthel Index original 10-item version; National Institutes of Health Stroke Scale); post-stroke depression (Patient Health Questionnaire-9; PHQ-9); and overall survival. Safety assessments include the evaluation of treatment-emergent adverse events; laboratory parameters; vital signs; electrocardiogram; suicidal ideation and behavior (PHQ-9 question 9). The protocol aimed to randomize approximately 200 patients (1:1), recruited from 21 sites in seven European countries and Israel. Despite the challenges encountered, particularly during the COVID-19 pandemic, the study progressed and included a remarkable number of patients, with 129 screened and 125 randomized. Recruitment was stopped after 30 months, the first patient entered in May 2019, and the study is ongoing and following up on patients according to the Clinical Trial Protocol.

ANCA-associated glomerulonephritis and lupus nephritis following COVID-19 vaccination: a case report and literature review.

With the coverage of COVID-19 vaccination, it has been possible to observe the potential side effects of SARS-CoV-2 vaccines, with the most common ones being fever, myalgia, headache, and fatigue. However, an association has been observed between new and recurrent kidney injuries, mainly glomerulonephritis and lupus nephritis associated with ANCA, with the Pfizer-BioNTech, Moderna, Sinovac, and AstraZeneca vaccines, although the relationship between them is not clear. We report a case of ANCA-related vasculitis and lupus glomerulonephritis after the second dose of the AstraZeneca vaccine. The elderly patient presented significant worsening of kidney function after immunosuppression and complications after a new onset COVID-19 infection that led to death. We provide a literature review about kidney damage related to ANCA vasculitis after COVID-19 vaccine, aiming for a better understanding of the pathophysiological mechanism of kidney injury, its presentation, and treatment.