RESUMEN

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.

RESUMEN

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.

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

RESUMEN

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%.

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Background: In the absence of direct therapy for COVID-19, extracorporeal blood treatment (EBT) could represent an option for cytokine removal. Objective: This study aimed to describe and compare cytokine removal during intermittent haemodialysis (IHD) and continuous renal replacement therapy (CRRT) in COVID-19 patients with Acute Kidney Injury (AKI). Methods: It was a cohort study that studied patients with COVID-19-related AKI according to KDIGO criteria and admitted at Intensive Care Unit (ICU). Blood samples were collected at the start and end of both IHD using high flux (HF) membranes (10 patients) and continuous venovenous haemodiafiltration (CVVHDF:10 patients) in two sessions for measuring 13 different plasma interleukins and calculating the cytokine removal rate. Results: There was no difference between the two groups regarding mechanical ventilation, vasoactive drug, age or prognostic scores. Patients treated by CRRT presented higher levels of IL-2 and IL-8 than patients treated by IHD at dialysis start. Cytokine removal ranged from 9% to 78%. Patients treated by CRRT presented higher cytokine removal for IL-2, IL-6 IL-8, IP-10 and TNF. The removal rates of IL-4, IL-10, IL-17A, IFN, MCP-1 and TGF-B1 were similar in two groups. After one session of CVVHDF (24 h), IL-2 and IL-1ß levels did not vary significantly, whereas IL-4, IL-6, IL-8, IL-10, IL-17A, TNF, IFN, IP-10, MCP-1, IL-12p70 and TGF-B1 decreased by 33.8-76%, and this decrease was maintained over the next 24 h. In IHD groups, IL-2, IL-6, TNF, IP-10 and IL-1ß levels did not decrease significantly whereas IL-4, IL-8, IL-10, IL-17A, IFN, MCP-1, IL-12p70 and TGF-B1 decreased by 21.8-72%; however, cytokine levels returned to their initial values after 24 h. Conclusion: Cytokine removal is lower in IHD using HF membranes than in CVVHDF, and in IHD the removal is transient and selective, which can be associated with mortality during cytokines storm-related COVID-19.

RESUMEN

Introduction: Elderly patients with COVID-19 are at a higher risk of severity and death as not only several comorbidities but also aging itself has been considered a relevant risk factor. Acute kidney injury (AKI), one of the worst complications of SARS-CoV-2 infection, is associated with worse outcomes. Studies on AKI with COVID-19 in Latin-American patients of older age remain scarce. Objectives: To determine AKI incidence and the risk factors associated with its development, as well as to compare outcome of elderly patients with or without AKI associated with SARS-CoV-2 infection. Methods: This retrospective cohort study evaluated patients with SARS-CoV2 infection admitted to a Public Tertiary Referral Hospital from 03/01/2020 to 12/31/2020, from admission to resolution (hospital discharge or death). Demographic, clinical, and laboratory data were collected from patients during hospitalization. Daily kidney function assessment was performed by measuring serum creatinine and urine output. AKI was diagnosed according to KDIGO 2012 criteria. Results: Of the 347 patients with COVID-19 admitted to our hospital during the study period, 52.16% were elderly, with a median age of 72 years (65- 80 years). In this age group, most patients were males (56.91%), hypertensive (73.48%), and required ICU care (55.25%). AKI overall incidence in the elderly was 56.9%, with higher frequency in ICU patients (p < 0.001). There was a predominance of KDIGO 3 (50.48%), and acute kidney replacement therapy (AKRT) was required by 47.57% of the patients. The risk factors associated with AKI development were higher baseline creatinine level (OR 10.54, CI 1.22 -90.61, p = 0.032) and need for mechanical ventilation (OR 9.26, CI 1.08-79.26, p = 0.042). Mortality was also more frequent among patients with AKI (46.41%vs24.7%, p < 0.0001), with death being associated with CPK level (OR 1.009, CI 1.001-1.017, p = 0.042), need for mechanical ventilation (OR 17.71, CI 1.13-277.62, p = 0.002) and KDIGO 3 (OR 2.017 CI 1.039 -3.917, p = 0.038). Conclusion: AKI was frequent among the elderly hospitalized with COVID-19 and its risk factors were higher baseline creatinine and need for mechanical ventilation. AKI was independently associated with a higher risk of death.

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

INTRODUCTION: The prevalence of epilepsy increases in elderly patients aged > 65 years, and treatment is challenging because clinical data are limited. OBJECTIVE: Our objective was to evaluate the safety of eslicarbazepine acetate (ESL) in patients aged ≥ 65 years versus non-elderly patients with focal seizures. METHODS: The safety data of seven phase II and III, double-blind, open-label, randomized clinical studies of ESL in adults were pooled. At least possibly related treatmentemergent adverse events (TEAEs) and ESL post-marketing adverse drug reactions (ADRs) were analyzed separately by age categories. RESULTS: The most frequently reported at least possibly related TEAEs in elderly (N = 120) versus non-elderly patients (N = 1863) were dizziness (10.8 vs. 20.3%), somnolence (9.2 vs. 12.6%), and hyponatremia (6.7 vs. 1.5%). Elderly patients presented a higher incidence of serious TEAEs (22.5 vs. 7.6%) and at least possibly related serious TEAEs (6.7 vs. 2.5%), probably because treatment was complicated by comorbidities and comedications. After an estimated cumulative exposure of over 2 million patient-months worldwide and 8 years of post-marketing surveillance, hyponatremia was the most frequently reported ADR (n = 232), accounting for 14.6% and 6.8% of the ADRs reported in elderly (n = 473) and non-elderly patients (n = 2406), respectively. This was followed by ADR/safety information such as drug-dose titration not performed (7.0 vs. 5.4%), product use in unapproved indication (4.9 vs. 1.9%), off-label use (3.4 vs. 2.2%), dizziness (3.4 vs. 3.5%), and seizure (2.1 vs. 5.8%). CONCLUSION: No specific safety issue was identified from the pooled studies for elderly compared with non-elderly patients. After 8 years of post-marketing surveillance, the qualitative safety of ESL remains similar to that observed in the clinical studies.

Asunto(s)

RESUMEN

Mammography has a crucial role in breast cancer detection. The National Cancer Institute (INCA) estimates that 29.7% of the cancer cases in Brazil are related specifically to the breast. It is necessary to evaluate the mean glandular dose with a new solid-state detector in a digital radiography system, utilizing PMMA phantoms and spacers for different thicknesses. The Selenia Dimensions (Hologic, Bedford) direct radiography (DR) system can perform full-field digital mammographies through digital detectors. This system uses new technologies, such as the digital breast tomosynthesis system (DBT), and employs a sequence of projections acquired over the breast, resulting in images with low contrast. The estimation of breast dose is an important part of mammographic quality control for x-ray mammography. Nevertheless, there are currently no standard protocols for the dosimetry of breast imaging in 3D. Additionally, a x-ray spectra function is crucial to measure a considerable output in x-ray spectrometry. The purpose of this work was to assess the mean glandular dose (MGD) and the spectra in slabs of polymethyl methacrylate (PMMA) and breast equivalent thickness through digital mammography using four experiments: a Hologic Selenia Dimensions mammograph with a solid-state detector; a spectrometer (only for the spectra, in this case); a clinical COMET x-ray tube with a solid-state detector; and the MCNPX code. References recommend that the real environments that work well with digital mammography are in the following tube voltages: 25 kVp; 26 kVp; 28 kVp; 31 kVp and 33 kVp. Taking into account several thicknesses of PMMA, the results of both the MGD in metrological, clinical and simulated cases were in accordance with the references, from 30 mm of PMMA. All the spectra for all cases have indicated good agreement with the references.

Asunto(s)

RESUMEN

PURPOSE: Mammography is the diagnostic imaging practice used in screening to detect early lesions suspected of malignancy. It uses a low energy X-ray beam in which a low dose in the order of 2-3 mGy is delivered to patient breast cells. However, it has been speculated that it could lead to significant cell damage, when compared to conventional X-ray. We investigated the biological effects of low doses, with mean glandular doses (MGDs) of 2.5 mGy and 2.5 + 2.5 mGy, on mammary cells in vitro. METHODS: We used the non-tumorigenic cell line (MCF-10A) and two tumor cells lines (MCF-7 and MDA-MB-231). Colony formation, apoptosis, and double-strand DNA breaks (DSBs) were quantified. RESULTS: The selected MGD regimens did not alter the formation of colonies by any of the cell lines. MCF-7 cells exhibited a markedly increase in apoptosis, 24 h after the single-dose protocol; MCF-10A cells underwent apoptosis only after 72 h, with both irradiation regimens, while MDA-MB-231 cells (highly invasive and metastatic) were not susceptible to apoptosis. The detection of γH2AX histone in the nuclei of irradiated cells showed that the double-dose resulted in increase of DSBs, especially in tumor cell lines. CONCLUSIONS: Although the health benefits of early breast screening remain indisputable, our future perspective is to better understand the biological basis for the effects of low dose radiation on breast cells and to investigate if and under what conditions there would be a risky situation in repeated mammography screening, in both asymptomatic and symptomatic women.

Asunto(s)

RESUMEN

Cobalt-60 irradiators and soft X-ray machines are frequently used for research purposes, but the dosimetry is not always performed using the recommended protocols. This may lead to confusing and untrustworthy results within the conducted research. Postal dosimetry systems have already been approved by the IAEA, with thermoluminescence dosimeters (TLD) and optically stimulated luminescence (OSL) as the most commonly used dosimeter systems in these cases. The present study tests the Fricke dosimeter properties as a potential system to be used in postal dosimetry for a project using research irradiators. The Fricke solution was prepared according to the literature, and the linearity and fading tests were performed accordingly. All calculated doses were measured using a NE2571 Farmer ionization chamber as a reference. Doses ranging from 25 to 300 Gy were delivered by a research irradiator, with 150 kV and 22 mA to the Fricke solutions inside polyethylene (PE) bags (4 × 4 × 0.2 cm3). The results compared with the ionization chamber showed a linear response to the range of doses used. Fading tests showed no significant difference for the absorbed doses over 9 days, with a maximum difference of 1.5% found between days 0 and 3. The Fricke dosimeter presented good linearity, for low and high doses, and low uncertainties for the fading even for 9 days after irradiation. These preliminary results are motivating, and as the next step, we intend to design a postal dosimetry system using the PE bags of Fricke solution.

Asunto(s)

RESUMEN

Renal involvement is frequent in COVID-19 (4-37%). This study evaluated the incidence and risk factors of acute kidney injury (AKI) in hospitalized patients with COVID-19. Methodology: This study represents a prospective cohort in a public and tertiary university hospital in São Paulo, Brazil, during the first 90 days of the COVID-19 pandemic, with patients followed up until the clinical outcome (discharge or death). Results: There were 101 patients hospitalized with COVID-19, of which 51.9% were admitted to the intensive care unit (ICU). The overall AKI incidence was 50%; 36.8% had hematuria or proteinuria (66.6% of those with AKI), 10.2% had rhabdomyolysis, and mortality was 36.6%. Of the ICU patients, AKI occurred in 77.3% and the mortality was 65.4%. The mean time for the AKI diagnosis was 6 ± 2 days, and Kidney Disease Improving Global Outcomes (KDIGO) stage 3 AKI was the most frequent (58.9%). Acute renal replacement therapy was indicated in 61.5% of patients. The factors associated with AKI were obesity [odds ratio (OR) 1.98, 95% confidence interval (CI) 1.04-2.76, p < 0.05] and the APACHE II score (OR 1.97, 95% CI 1.08-2.64, p < 0.05). Mortality was higher in the elderly (OR 1.03, 95% CI 1.01-1.66, p < 0.05), in those with the highest APACHE II score (OR 1.08, 95% CI 1.02-1.98, p < 0.05), and in the presence of KDIGO stage 3 AKI (OR 1.11, 95% CI 1.05-2.57, p < 0.05). Conclusion: AKI associated with severe COVID-19 in this Brazilian cohort was more frequent than Chinese, European, and North American data, and the risk factors associated with its development were obesity and higher APACHE II scores. Mortality was high, mainly in elderly patients, in those with a more severe disease manifestation, and in those who developed KDIGO stage 3 AKI.

RESUMEN

PURPOSE: The Fricke dosimeter has been shown to be a viable option as an absorbed dose standard. This work aims to provide the dose distribution in an irradiator container during blood irradiation using Fricke dosimetry. METHODS: Measurements were performed using a Gammacell Elan 3000 blood irradiator at Hemocenter in Rio de Janeiro, Brazil. A specific phantom was constructed and patented by the authors to perform these measurements. Fricke solution was prepared according to international protocols, and polyethylene bags filled with Fricke solution (n = 19) were spatially distributed within the phantom. Control bags were also submitted to the same process, except the irradiation. The irradiation time was calculated to give 25.7 Gy to the central portion of the phantom, the same dose used for blood bags. RESULTS: Encouraging results were obtained with an overall uncertainty of 2.1% (k = 1). The obtained results were compared with the doses calculated by the physicist from Hemocenter based on parameters provided by the manufacturer. The mean dose delivered to the Fricke bag in the center of the phantom (cavity 2) was 28.7 ± 0.5 Gy, which is 12% higher than the planned dose of 25.7 Gy. CONCLUSIONS: The obtained results showed that the setup (Fricke and phantom) is able to perform dosimetry for blood irradiators. The delivered dose was higher than expected. This highlights the importance in controlling all the parameters during irradiation to ensure the correct dose for all irradiated bags.

Asunto(s)