Resveratrol (RSV) is a natural antioxidant commonly found in grapes, berries, and nuts that has shown promising results in the treatment of a variety of degenerative and age-related diseases. Despite ...the proven beneficial results on reduction of reactive oxidant species (ROS) and on inflammatory process, RSV shows various limitations including low long-term stability, aqueous solubility, and bioavailability, restricting its applications in the medical-pharmaceutical area. To overcome these limitations, it has been applied in pharmaceutical formulations as nanostructured lipid carriers (NLC). Thus, the present study focuses on the optimization of the production process of NLC. NLC was produced by high shear homogenization (HSH) and ultrasound method (US) using Compritol® ATO C888 as solid lipid and Miglyol 812® as liquid lipid. In order to obtain an optimized formulation, we used a 22 full factorial design with triplicate of central point investigating the effects of the production process parameters; shear intensity and homogenization time, on the mean particle size (PS) and polydispersity index (PDI). Instability index, encapsulation efficiency, and production yield were also evaluated. As the PS and PDI values obtained with 6 min of shear at 19,000 rpm and 10 min of shear and 24,000 rpm were similar, the instability index (<0.1) was also used to select the optimal parameters. Based on the results of the experimental design and instability index, it was concluded that the shear rate of 19,000 rpm and the shear time of 6 min are the optimal parameters for RSV-loaded NLC production. Factorial design contributed therefore to optimize the variables of the NLC production process from a small number of experiments.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly in Manaus, the capital of Amazonas state in northern Brazil. The attack rate there is an estimate of the final size of the ...largely unmitigated epidemic that occurred in Manaus. We use a convenience sample of blood donors to show that by June 2020, 1 month after the epidemic peak in Manaus, 44% of the population had detectable immunoglobulin G (IgG) antibodies. Correcting for cases without a detectable antibody response and for antibody waning, we estimate a 66% attack rate in June, rising to 76% in October. This is higher than in São Paulo, in southeastern Brazil, where the estimated attack rate in October was 29%. These results confirm that when poorly controlled, COVID-19 can infect a large proportion of the population, causing high mortality.
Since 2022, monkeypox virus (MPXV) has been causing a multinational epidemic with Brazil as one of the most affected countries.1,2 During the current mpox (formally known as monkeypox) epidemic, men ...with AIDS are at increased risk of severe illness and death, although it remains unclear whether deaths are directly attributed to MPXV.2 We report clinical and autopsy findings of two men in their early 20s, who had severe mpox associated with AIDS in São Paulo. The pathology of mpox described here is severe and includes new findings of visceral involvement by MPXV (figure and appendix pp 8–11).3–6 In both cases, autopsies showed anasarca, cavity effusions, and diffuse MPXV-mediated lesions in various organs confirmed by detectable vaccinia antigens and MPXV-DNA. Besides multiple MPXV-skin lesions with necrotic ulcers and MPXV-dermal vasculitis, the autopsies showed MPXV-induced bilateral necrotising nodular pneumonia, acute pleuritis with pleural effusion, nodular ulcerative gastrointestinal lesions, necrotic glossitis with vasogenic oedema, extensive proctitis, pancreatitis, sialoadenitis, orchitis (including germinative cells within seminiferous tubules), epididymitis, adrenalitis, and haemophagocytosis. ...in cases of HIV and MPXV coinfection, MPXV appears to be transmitted by a complex mechanism involving contact with infected skin and mucosa, and respiratory and sexual transmission, corroborating previous data on aerosol MPVX animal infection and MPXV–DNA detection in semen.8–12 These autopsies show previously undescribed findings in the pathology of human MPXV infection and are helpful to understand why people living with HIV or AIDS are under high risk for worse mpox-associated outcomes.13–15 We declare no competing interests.
Polyelectrolyte nanocomposites rarely reach a stable state and aggregation often occurs. Here, we report the synthesis of nanocomposites for the oral delivery of insulin composed of alginate, dextran ...sulfate, poly-(ethylene glycol) 4000, poloxamer 188, chitosan, and bovine serum albumin. The nanocomposites were obtained by Ca
-induced gelation of alginate followed by an electrostatic-interaction process among the polyelectrolytes. Chitosan seemed to be essential for the final size of the nanocomposites and there was an optimal content that led to the synthesis of nanocomposites of 400-600 nm hydrodynamic size. The enhanced stability of the synthesized nanocomposites was assessed with LUMiSizer after synthesis. Nanocomposite stability over time and under variations of ionic strength and pH were assessed with dynamic light scattering. The rounded shapes of nanocomposites were confirmed by scanning electron microscopy. After loading with insulin, analysis by HPLC revealed complete drug release under physiologically simulated conditions.
With the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants that may increase transmissibility and/or cause escape from immune responses, there is an urgent need for ...the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant, first detected in the United Kingdom, could be serendipitously detected by the Thermo Fisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69-70, would cause a "spike gene target failure" (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern (VOC) that lack spike Δ69-70, such as B.1.351 (also 501Y.V2), detected in South Africa, and P.1 (also 501Y.V3), recently detected in Brazil. We identified a deletion in the ORF1a gene (ORF1a Δ3675-3677) in all 3 variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675-3677 as the primary target and spike Δ69-70 to differentiate, we designed and validated an open-source PCR assay to detect SARS-CoV-2 VOC. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, and P.1.
The emergence of diverse lineages harboring mutations with functional significance and potentially enhanced transmissibility imposes an increased difficulty on the containment of the SARS-CoV-2 ...pandemic ....
Resveratrol (RSV) is a natural antioxidant commonly found in grapes, berries, and nuts that has shown promising results in the treatment of a variety of degenerative and age-related diseases. Despite ...the proven beneficial results on reduction of reactive oxidant species (ROS) and on inflammatory process, RSV shows various limitations including low long-term stability, aqueous solubility, and bioavailability, restricting its applications in the medical-pharmaceutical area. To overcome these limitations, it has been applied in pharmaceutical formulations as nanostructured lipid carriers (NLC). Thus, the present study focuses on the optimization of the production process of NLC. NLC was produced by high shear homogenization (HSH) and ultrasound method (US) using Compritol
ATO C888 as solid lipid and Miglyol 812
as liquid lipid. In order to obtain an optimized formulation, we used a 2
full factorial design with triplicate of central point investigating the effects of the production process parameters; shear intensity and homogenization time, on the mean particle size (PS) and polydispersity index (PDI). Instability index, encapsulation efficiency, and production yield were also evaluated. As the PS and PDI values obtained with 6 min of shear at 19,000 rpm and 10 min of shear and 24,000 rpm were similar, the instability index (<0.1) was also used to select the optimal parameters. Based on the results of the experimental design and instability index, it was concluded that the shear rate of 19,000 rpm and the shear time of 6 min are the optimal parameters for RSV-loaded NLC production. Factorial design contributed therefore to optimize the variables of the NLC production process from a small number of experiments.
The present report addresses the development of cutaneous and ocular reactions possibly related to meloxicam administration in a dog. Based on clinical signs and absence of laboratory data compatible ...with the other differential diagnoses considered, the possibility of an adverse drug reaction (ADR) due to meloxicam was considered. Skin biopsy revealed haemorrhage of the superficial and deep dermis, associated with hyperplasia of endothelial cells and epidermal sloughing. Vasculitis in the deep dermis was also noted. Such lesions were considered compatible with an ADR. Although the owner was not aware of any previous allergic reaction to drugs, the animal had a clinical history of atopic dermatitis. Meloxicam is a nonsteroid anti-inflammatory drug (NSAID) in the oxicam family, indicated for the control of inflammation and pain in acute and chronic musculoskeletal disorders in dogs. Although meloxicam is usually well tolerated, the present clinical case represents an alert to practitioners about the potential role of NSAIDS in ADRs in dogs with a history of allergic cutaneous diseases.
IntroductionLittle evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in São ...Paulo state, Brazil, and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities.MethodsWe conducted a cross-sectional study using hospitalised severe acute respiratory infections notified from March to August 2020 in the Sistema de Monitoramento Inteligente de São Paulo database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple data sets for individual-level and spatiotemporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour and comorbidities.ResultsThroughout the study period, patients living in the 40% poorest areas were more likely to die when compared with patients living in the 5% wealthiest areas (OR: 1.60, 95% CI 1.48 to 1.74) and were more likely to be hospitalised between April and July 2020 (OR: 1.08, 95% CI 1.04 to 1.12). Black and Pardo individuals were more likely to be hospitalised when compared with White individuals (OR: 1.41, 95% CI 1.37 to 1.46; OR: 1.26, 95% CI 1.23 to 1.28, respectively), and were more likely to die (OR: 1.13, 95% CI 1.07 to 1.19; 1.07, 95% CI 1.04 to 1.10, respectively) between April and July 2020. Once hospitalised, patients treated in public hospitals were more likely to die than patients in private hospitals (OR: 1.40%, 95% CI 1.34% to 1.46%). Black individuals and those with low education attainment were more likely to have one or more comorbidities, respectively (OR: 1.29, 95% CI 1.19 to 1.39; 1.36, 95% CI 1.27 to 1.45).ConclusionsLow-income and Black and Pardo communities are more likely to die with COVID-19. This is associated with differential access to quality healthcare, ability to self-isolate and the higher prevalence of comorbidities.
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