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1.
Pharm Res ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720034

RESUMEN

PURPOSE: The goal was to assess, for lipophilic drugs, the impact of logP on human volume of distribution at steady-state (VDss) predictions, including intermediate fut and Kp values, from six methods: Oie-Tozer, Rodgers-Rowland (tissue-specific Kp and only muscle Kp), GastroPlus, Korzekwa-Nagar, and TCM-New. METHOD: A sensitivity analysis with focus on logP was conducted by keeping pKa and fup constant for each of four drugs, while varying logP. VDss was also calculated for the specific literature logP values. Error prediction analysis was conducted by analyzing prediction errors by source of logP values, drug, and overall values. RESULTS: The Rodgers-Rowland methods were highly sensitive to logP values, followed by GastroPlus and Korzekwa-Nagar. The Oie-Tozer and TCM-New methods were only modestly sensitive to logP. Hence, the relative performance of these methods depended upon the source of logP value. As logP values increased, TCM-New and Oie-Tozer were the most accurate methods. TCM-New was the only method that was accurate regardless of logP value source. Oie-Tozer provided accurate predictions for griseofulvin, posaconazole, and isavuconazole; GastroPlus for itraconazole and isavuconazole; Korzekwa-Nagar for posaconazole; and TCM-New for griseofulvin, posaconazole, and isavuconazole. Both Rodgers-Rowland methods provided inaccurate predictions due to the overprediction of VDss. CONCLUSIONS: TCM-New was the most accurate prediction of human VDss across four drugs and three logP sources, followed by Oie-Tozer. TCM-New showed to be the best method for VDss prediction of highly lipophilic drugs, suggesting BPR as a favorable surrogate for drug partitioning in the tissues, and which avoids the use of fup.

2.
Int J Womens Health ; 16: 663-678, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650835

RESUMEN

Previously considered a skin disease exclusively affecting adolescents, characterized by inflammatory and non-inflammatory skin lesions, acne vulgaris is now increasingly observed in adult life, including post-menopause. Today, adult female acne (AFA) is a common chronic inflammatory disease of the pilosebaceous unit, with polymorphic lesions presenting as open or closed comedones, papules, pustules, and even nodules or cysts, often with the presence of sequelae. AFA may persist from adolescence or manifest de novo in adulthood. Its etiology is multifactorial, involving genetic, hormonal, dietary, and environmental factors, yet still incompletely understood. Increased sebum production, keratinocyte hyper-proliferation, inflammation, and reduced diversity of Cutibacterium acnes strains are the underlying disease mechanisms. During menopausal transition, a relative increase in androgen levels occurs, just as estrogens begin to decline, which can manifest itself as acne. Whereas most AFA exhibit few acne lesions with normo-androgenic serum levels, baseline investigations including androgen testing panel enable associated comorbidities to be eliminated, such as polycystic ovarian syndrome, congenital adrenal hyperplasia, or tumors. Another interesting feature is AFA's impact on quality of life, which is greater than in adolescents, being similar to other chronic diseases like asthma. The therapeutic approach to AFA depends on its severity and associated features. This review investigates the intricate facets of AFA, with a specific focus on incidence rates, treatment modalities, and the curious impact of menopause. Utilizing insights from contemporary literature and scientific discussions, this article seeks to advance our understanding of AFA, offering new perspectives to shape clinical practices and improve patient outcomes.

4.
Int J Biol Macromol ; 259(Pt 2): 129157, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199539

RESUMEN

Oral cancer incidence and mortality are increasing over time. The most common therapies for oral cancers are surgery and radiotherapy, either used alone or combined, and immunotherapy can be also an option. Although there are several therapeutic options, none of them are completely effective, and in addition, there are numerous associated side effects. To overcome these limitations, researchers have been trying to reduce these drawbacks by using drug delivery systems that carry drugs for specific delivery to cancer cells. For that purpose, RNA-coated liposomes to selectively deliver the ligands C8 (acridine orange derivative) and dexamethasone to oral cancer cells were produced, characterized, and biologically evaluated. Firstly, the RNA structure and binding interaction with ligands (C8 and dexamethasone) were evaluated by circular dichroism (CD), thermal difference spectroscopy (TDS), nuclear magnetic resonance (NMR) and fluorescence titrations. The biophysical assays evidenced the formation of an RNA hairpin and duplex structure. Moreover, steady-state and time-resolved fluorescence intensity and anisotropy experiments show that C8 forms a complex with RNA and adopts an open conformation upon RNA binding. Then, RNA-coated liposomes were characterized by dynamic light scattering, and diameters near 160 nm were observed. Time-resolved anisotropy measurements of C8 loaded in RNA-functionalized liposomes indicate the co-existence of free C8 in solution (inside the liposome) and C8 bound to RNA at the external liposome surface. The RNA-functionalized liposomes loaded with C8 or dexamethasone mediated a significant reduction in the cell viability of malignant UPCI-SCC-154 cells while maintaining viable non-malignant NHDF cells. Additionally, the liposomes were able to internalize the cells, with higher uptake by the malignant cell line. Overall, the results obtained in this work can contribute to the development of new drug delivery systems based on RNA-coated liposomes.


Asunto(s)
Liposomas , Neoplasias de la Boca , Humanos , Liposomas/química , Sistemas de Liberación de Medicamentos , Línea Celular , Neoplasias de la Boca/tratamiento farmacológico , Dexametasona/farmacología
5.
Protein Sci ; 33(1): e4835, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37984447

RESUMEN

Pulmonary surfactant (PS) is a lipid-protein complex that forms films reducing surface tension at the alveolar air-liquid interface. Surfactant protein C (SP-C) plays a key role in rearranging the lipids at the PS surface layers during breathing. The N-terminal segment of SP-C, a lipopeptide of 35 amino acids, contains two palmitoylated cysteines, which affect the stability and structure of the molecule. The C-terminal region comprises a transmembrane α-helix that contains a ALLMG motif, supposedly analogous to a well-studied dimerization motif in glycophorin A. Previous studies have demonstrated the potential interaction between SP-C molecules using approaches such as Bimolecular Complementation assays or computational simulations. In this work, the oligomerization state of SP-C in membrane systems has been studied using fluorescence spectroscopy techniques. We have performed self-quenching and FRET assays to analyze dimerization of native palmitoylated SP-C and a non-palmitoylated recombinant version of SP-C (rSP-C) using fluorescently labeled versions of either protein reconstituted in different lipid systems mimicking pulmonary surfactant environments. Our results reveal that doubly palmitoylated native SP-C remains primarily monomeric. In contrast, non-palmitoylated recombinant SP-C exhibits dimerization, potentiated at high concentrations, especially in membranes with lipid phase separation. Therefore, palmitoylation could play a crucial role in stabilizing the monomeric α-helical conformation of SP-C. Depalmitoylation, high protein densities as a consequence of membrane compartmentalization, and other factors may all lead to the formation of protein dimers and higher-order oligomers, which could have functional implications under certain pathological conditions and contribute to membrane transformations associated with surfactant metabolism and alveolar homeostasis.


Asunto(s)
Proteína C Asociada a Surfactante Pulmonar , Surfactantes Pulmonares , Proteína C Asociada a Surfactante Pulmonar/química , Proteína C Asociada a Surfactante Pulmonar/metabolismo , Surfactantes Pulmonares/química , Surfactantes Pulmonares/metabolismo , Transferencia Resonante de Energía de Fluorescencia , Lípidos/química , Tensoactivos
6.
Parasit Vectors ; 16(1): 415, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37964392

RESUMEN

BACKGROUND: Tick control is a worldwide challenge due to its resistance to acaricides. Essential oils (EOs) and isolated compounds (EOCs) are potential alternatives for tick control technologies. METHODS: A review with EOs and EOCs, under field and semi-field conditions, was performed based on Scopus, Web of Science and PubMed databases. Thirty-one studies published between 1991 and 2022 were selected. The search was performed using the following keywords: "essential oil" combined with "tick," "Ixodes," "Argas," "Rhipicephalus," "Amblyomma," "Hyalomma," "Dermacentor," "Haemaphysalis" and "Ornithodoros." The words "essential oil" and "tick" were searched in the singular and plural. RESULTS: The number of studies increased over the years. Brazil stands out with the largest number (51.6%) of publications. The most studied tick species were Rhipicephalus microplus (48.4%), Ixodes scapularis (19.4%), Amblyomma americanum and R. sanguineus sensu lato (9.7% each). Cattle (70%) and dogs (13%) were the main target animal species. Regarding the application of EOs/EOCs formulations, 74% of the studies were conducted with topical application (spray, pour-on, foam, drop) and 26% with environmental treatment (spray). Efficacy results are difficult to evaluate because of the lack of information on the methodology and standardization. The nanotechnology and combination with synthetic acaricides were reported as an alternative to enhance the efficacy of EOs/EOCs. No adverse reactions were observed in 86.6% of the studies evaluating EOs/EOCs clinical safety. Studies regarding toxicity in non-target species and residues are scarce. CONCLUSIONS: This article provides a comprehensive review on the use of EOs and EOCs to reduce tick infestations, in both the hosts and the environment. As future directions, we recommend the chemical characterization of EOs, methodology standardization, combination of EOs/EOCs with potential synergists, nanotechnology for new formulations and safety studies for target and non-target organisms, also considering the environmental friendliness.


Asunto(s)
Acaricidas , Enfermedades de los Bovinos , Enfermedades de los Perros , Ixodes , Ixodidae , Aceites Volátiles , Rhipicephalus , Infestaciones por Garrapatas , Animales , Perros , Bovinos , Aceites Volátiles/química , Acaricidas/farmacología , Acaricidas/uso terapéutico , Infestaciones por Garrapatas/tratamiento farmacológico , Infestaciones por Garrapatas/prevención & control , Infestaciones por Garrapatas/veterinaria , Amblyomma , Control de Ácaros y Garrapatas/métodos , Enfermedades de los Bovinos/tratamiento farmacológico , Enfermedades de los Perros/tratamiento farmacológico
7.
AAPS J ; 25(6): 103, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37936002

RESUMEN

The in-person workshop "Drug Dissolution in Oral Drug Absorption" was held on May 23-24, 2023, in Baltimore, MD, USA. The workshop was organized into lectures and breakout sessions. Three common topics that were re-visited by various lecturers were amorphous solid dispersions (ASDs), dissolution/permeation interplay, and in vitro methods to predict in vivo biopharmaceutics performance and risk. Topics that repeatedly surfaced across breakout sessions were the following: (1) meaning and assessment of "dissolved drug," particularly of poorly water soluble drug in colloidal environments (e.g., fed conditions, ASDs); (2) potential limitations of a test that employs sink conditions for a poorly water soluble drug; (3) non-compendial methods (e.g., two-stage or multi-stage method, dissolution/permeation methods); (4) non-compendial conditions (e.g., apex vessels, non-sink conditions); and (5) potential benefit of having both a quality control method for batch release and a biopredictive/biorelevant method for biowaiver or bridging scenarios. An identified obstacle to non-compendial methods is the uncertainty of global regulatory acceptance of such methods.


Asunto(s)
Biofarmacia , Absorción Intestinal , Humanos , Liberación de Fármacos , Solubilidad , Agua
8.
ACS Infect Dis ; 9(10): 1889-1900, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37669146

RESUMEN

The formation of biofilms is a common virulence factor that makes bacterial infections difficult to treat and a major human health problem. Biofilms are bacterial communities embedded in a self-produced matrix of extracellular polymeric substances (EPS). In this work, we show that vCPP2319, a polycationic peptide derived from the capsid protein of Torque teno douroucouli virus, is active against preformed Staphylococcus aureus biofilms produced by both a reference strain and a clinical strain isolated from a diabetic foot infection, mainly by the killing of biofilm-embedded bacteria. The direct effect of vCPP2319 on bacterial cells was imaged using atomic force and confocal laser scanning microscopy, showing that the peptide induces morphological changes in bacterial cells and membrane disruption. Importantly, vCPP2319 exhibits low toxicity toward human cells and high stability in human serum. Since vCPP2319 has a limited effect on the biofilm EPS matrix itself, we explored a combined effect with α-amylase (EC 3.2.1.1), an EPS matrix-degrading enzyme. In fact, α-amylase decreases the density of S. aureus biofilms by 2.5-fold. Nonetheless, quantitative analysis of bioimaging data shows that vCPP2319 partially restores biofilm compactness after digestion of the polysaccharides, probably due to electrostatic cross-bridging of the matrix nucleic acids, which explains why α-amylase fails to improve the antibacterial action of the peptide.


Asunto(s)
Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Péptidos Antimicrobianos , Biopelículas , Infecciones Estafilocócicas/microbiología , alfa-Amilasas/farmacología , alfa-Amilasas/uso terapéutico
9.
Int J Pharm ; 644: 123325, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37591472

RESUMEN

Reliable, experimentally determined partition coefficient P (logP) for most drugs are often unavailable in the literature. Many values are from in silico predictions and may not accurately reflect drug lipophilicity. In this study, a robust, viable, and resource sparing method to measure logP was developed using reverse phase high performance liquid chromatography (RP-HPLC). The logP of twelve common drugs was measured using calibration curves at pH 6 and 9 that were created using reference standards with well-established logP. The HPLC method reported here can be used for high throughput estimation of logP of commonly used drugs. LogP values here showed general agreement with the other few HPLC-based literature logP values available. Additionally, the HPLC-based logP values found here agreed partially with literature logP values found using other methodologies (±10%). However, there was no strong agreement since there are few experimentally determined literature logP values. This paper shows a facile method to estimate logP without using octanol or computational approaches. This method has excellent promise to provide reliable logP values of commonly used drugs available in literature. A larger pool of reliable logP values of commonly drugs has promise to improve quality of medicinal chemistry and pharmacokinetic (PK) models.


Asunto(s)
Química Farmacéutica , Cromatografía Líquida de Alta Presión , Calibración , Octanoles
10.
J Pharm Biomed Anal ; 234: 115505, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37393691

RESUMEN

A high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of itraconazole (ITZ) and hydroxyitraconazole (ITZ-OH) as part of a human pharmacokinetic study of novel tablet formulations. We demonstrated that 100 µL of plasma sample can be used with a protein precipitation extraction by optimizing different composition of acid in organic solvent for the precipitation solvent, giving comparable recovery to more time-consuming liquid-liquid or solid phase extractions. Additionally, we have shown that by monitoring the halogen isotopic peak for ITZ as well as optimizing chromatographic conditions, we are able to avoid carryover and endogenous interferences, allowing for a lower limit of quantification for our study. We validated the method to quantify ITZ and ITZ-OH from 1 to 250 ng/mL in human plasma and applied this to a formulation research clinical study (NCT04035187). This is the first itraconazole study to demonstrate robustness of the assay by performing interference testing of over-the-counter and common co-administered medications. We are also the first publication to perform incurred sample reanalysis (ISR) at the conclusion of a 672 sample clinical study to show reproducibility of assay performance.


Asunto(s)
Itraconazol , Espectrometría de Masas en Tándem , Humanos , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Reproducibilidad de los Resultados
11.
Front Cardiovasc Med ; 10: 1149717, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37363091

RESUMEN

Early-onset atrial fibrillation (AF) can be the manifestation of a genetic atrial myopathy. However, specific genetic identification of a mutation causing atrial fibrosis is rare. We report a case of a young patient with an asymptomatic AF, diagnosed during a routine examination. The cardiac MRI revealed extensive atrial fibrosis and the electrophysiology study showed extensive areas of low voltage. The genetic investigation identified a homozygous pathogenic variant in the NPPA gene in the index case and the presence of the variant in heterozygosity in both parents.

12.
Vet Parasitol ; 319: 109938, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37167691

RESUMEN

The aim of this study was to evaluate the reproductive biology and histopathology of the ovaries of engorged females of Rhipicephalus sanguineus sensu lato exposed to combinations of thymol and eugenol, as well as to evaluate in silico the possible interactions of thymol and eugenol in tick cell membranes. To evaluate the tick reproductive biology, the adult immersion test (AIT) was performed, in which the engorged females were immersed in solutions of thymol and eugenol, combined or alone, at concentrations of 2.5 and 5.0 mg/mL. Two control groups (water and 3% DMSO) were also performed. The ticks were kept in a controlled chamber (B.O.D - 27 ± 1 °C and 80% ± 5% RH) to evaluate egg production and viability. To perform the ovaries histopathological evaluation, females were immersed in combination of thymol and eugenol (each at 2.5 and 5.0 mg/mL) and control (water and 3% DMSO) solutions. After immersion, the females were kept in B.O.D (27 ± 1 °C and RH of 80% ± 5%) for four days, they were dissected and the ovaries processed for histological analysis. In addition, an in silico analysis was performed using PASS online® software to predict probability activity (PA) of thymol and eugenol in cell membranes. The treatment with the combination of thymol and eugenol (each at 5.0 mg/mL) caused a reduction (p < 0.01) in oviposition, while the treatments with thymol (5.0 mg/mL) and combination of thymol and eugenol (5.0 mg/mL) reduced (p < 0.05) the egg viability. The treatment with combination of thymol and eugenol (5.0 mg/mL) resulted in a control percentage of 99.9%, while in the other treatments, control percentages below 56% were observed. Oocytes from the females exposed to the combinations of thymol and eugenol (each compound at 2.5 mg/mL) showed histopathological changes, except on oocyte V, while those treated with these compounds alone at 2.5 mg/mL, did not reveal any change. Changes in the shape of the oocyte, presence of vacuoles in the cytoplasm and germinal vesicle, reduction and fusion of yolk granules and rupture of some oocytes were observed. In silico analysis, showed that these compounds can act as membrane permeability inhibitors, membrane permeability agonists, membrane integrity antagonists and apoptosis agonists. We conclude that the combination of thymol and eugenol causes changes in the reproductive biology and morphophysiology of engorged females oocytes. The in silico analysis using thymol and eugenol revealed the possibility of disorganization in the cell membranes, a fact that may explain the histopathological alterations observed.


Asunto(s)
Acaricidas , Rhipicephalus sanguineus , Rhipicephalus , Femenino , Animales , Timol/farmacología , Eugenol/farmacología , Dimetilsulfóxido , Acaricidas/farmacología
13.
Ticks Tick Borne Dis ; 14(4): 102190, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37167772

RESUMEN

The present study compared the efficacy of different methods to apply an acaricide formulation to control Rhipicephalus (Boophilus) microplus. To compare the methods, an acaricide blend containing three active ingredients (a pyrethroid and two organophosphates) was used. In experiment 1 (farm 1: Goiânia, GO, Brazil), three methods were tested: a backpack sprayer (BS), power sprayer (PS) and spray race (SR). In experiment 2 (farm 2: São José do Rio Pardo, SP, Brazil), two methods were tested: BS and PS. In both experiments, 10 cattle with similar tick burdens were used. On day 0 in both experiments, the animals were treated with the acaricide. On day +1 (only in experiment 1), +3, +7, +14, +21, +28 and +35 (only in experiment 2), tick counts were performed to determine the control efficacy. The time application, pressure (KPa), volume applied (L) and ergonomic aspects of each spraying system were also evaluated. The adult immersion test (AIT) using three different acaricide blends (combinations of pyrethroid + organophosphate) was performed to compare the susceptibility of strains of each farm. In experiment 1, all treatments significantly reduced (p < 0.05) the number of ticks on the animals, and PS resulted in the greatest acaricide efficacy since day +1. In experiment 2, both treatments (PS and BS) reduced (p < 0.05) the tick burden, and as observed in experiment 1, PS resulted in the best reduction. The application times were 4.5, 150 and 330 s, while pressures were 306.8, 4,826.3 and 220.6 KPa for SR, PS and BS, respectively. In the AIT, the efficacy values were between 99.8 and 100% for the tick strain form farm 1 (Goiânia), while for tick strain from farm 2 (São José do Rio Pardo), the efficacy was between 67.2 and 80.9%. We conclude that the sprayer methods chosen influences the efficacy of the acaricide. All sprayer methods were efficient for acaricide application; the best efficacy was obtained using the PS, while the SR resulted in good efficacy and lower application time. The strain from farm 2 was less susceptible to all acaricides tested.


Asunto(s)
Acaricidas , Enfermedades de los Bovinos , Piretrinas , Rhipicephalus , Infestaciones por Garrapatas , Animales , Bovinos , Acaricidas/farmacología , Piretrinas/farmacología , Organofosfatos , Brasil , Enfermedades de los Bovinos/prevención & control , Infestaciones por Garrapatas/prevención & control , Infestaciones por Garrapatas/veterinaria
15.
Rural Remote Health ; 23(1): 8178, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36802799

RESUMEN

INTRODUCTION: Climate change is a topic of growing interest and should guide our actions in society. Clinical practice must improve sustainability and ecological behavior as an opportunity. We intend to show how measures were implemented to reduce resource consumption in a health center in Gonçalo, a small village in the center of Portugal, with the support of local government spreading these practices across the community. METHODS: The first step was to account for daily resource use in Gonçalo's Health Center. Opportunities for improvement were listed in a multidisciplinary team meeting and subsequently implemented. Local government was very cooperative in the implementation of such measures, helping us spread the intervention to the community. RESULTS: A considerable reduction in resource consumption was verified, mainly the reduction of consumption of paper. Before this intervention, there was neither separation nor recycling of waste, which was initiated by this program. This change was implemented in the building of the Parish Council, at the Health Center and School Center of Gonçalo, where health education activities were promoted. DISCUSSION: In a rural area, the health center is an integral part of the life of the community in which it operates. Thus, their behaviors have the power to influence that same community. By showing our interventions and through practical examples, we intend to influence other health units to be an agent for change within their communities. By reducing, reusing and recycling, we intend to be a role model.


Asunto(s)
Educación en Salud , Humanos , Cambio Climático , Servicios de Salud Rural , Portugal , Desarrollo Sostenible
16.
Rural Remote Health ; 23(1): 8177, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36802825

RESUMEN

INTRODUCTION: Gonçalo, a village with 1316 inhabitants of which 573 are 65 years old or older, presents itself as the 'Cradle of Fine Basketry'. Its population, rich in culture and stories to tell, has the support of a day care center for the elderly, where around 20 elderly people spend their days and find social connection. These patients make individual trips to access medical and nursing consultations. METHODS: Creation of a monthly consultation at the day care center for the elderly patients there. RESULTS: Reduction in the number of individual trips by the elderly patients, through the displacement of the family team;Optimizing the management of each individual health plan with the support of the day center's technical director, including therapeutic management and carrying out complementary diagnostic tests;Observation of the elderly patients in a safer way, avoiding traveling and maintaining a familiar space;Closer ties between the elderly patients and healthcare team; and Training of day care center professionals. DISCUSSION: At the heart of the practice of a healthcare team is the health and well-being of each patient. Therefore, meeting their needs, reallocating resources and involving the community will lead to health gains. The 'Consultas em Dia' project reflects this same onjective: the need of each elderly person to have access to GP/family nurse consultations joined with the healthcare team's willingness to provide an adapted response. Together we improved access and care delivery … we improved the health of our community!


Asunto(s)
Centros de Día , Atención a la Salud , Humanos , Anciano , Niño , Guarderías Infantiles
17.
BMC Health Serv Res ; 23(1): 198, 2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36829122

RESUMEN

BACKGROUND: The COVID-19 pandemic raised awareness of the need to better understand where and how patient-level costs are incurred in health care organizations, as health managers and other decision-makers need to plan and quickly adapt to the increasing demand for health care services to meet patients' care needs. Time-driven activity-based costing offers a better understanding of the drivers of cost throughout the care pathway, providing information that can guide decisions on process improvement and resource optimization. This study aims to estimate COVID-19 patient-level hospital costs and to evaluate cost variability considering the in-hospital care pathways of COVID-19 management and the patient clinical classification. METHODS: This is a prospective cohort study that applied time-driven activity-based costing (TDABC) in a Brazilian reference center for COVID-19. Patients hospitalized during the first wave of the disease were selected for their data to be analyzed to estimate in-hospital costs. The cost information was calculated at the patient level and stratified by hospital care pathway and Ordinal Scale for Clinical Improvement (OSCI) category. Multivariable analyses were applied to identify predictors of cost variability in the care pathways that were evaluated. RESULTS: A total of 208 patients were included in the study. Patients followed five different care pathways, of which Emergency + Ward was the most followed (n = 118, 57%). Pathways which included the intensive care unit presented a statistically significant influence on costs per patient (p <  0.001) when compared to Emergency + Ward. The median cost per patient was I$2879 (IQR 1215; 8140) and mean cost per patient was I$6818 (SD 9043). The most expensive care pathway was the ICU only, registering a median cost per patient of I$13,519 (IQR 5637; 23,373) and mean cost per patient of I$17,709 (SD 16,020). All care pathways that included the ICU unit registered a higher cost per patient. CONCLUSIONS: This is one of the first microcosting study for COVID-19 that applied the TDABC methodology and demonstrated how patient-level costs vary as a function of the care pathways followed by patients. These findings can be used to develop value reimbursement strategies that will inform sustainable health policies in middle-income countries such as Brazil.


Asunto(s)
COVID-19 , Vías Clínicas , Humanos , Brasil , Estudios Prospectivos , Pandemias , Factores de Tiempo , Costos de Hospital , Hospitales , Hospitalización , Costos de la Atención en Salud
18.
Curr Med Chem ; 30(22): 2480-2517, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36200214

RESUMEN

Genistein (4',5,7-trihydroxyisoflavone) is a natural plant-derived phytoestrogen that can be found, for example, in soybean seeds. Genistein is present mainly in the human diet and is a common precursor in the antimicrobial phytoalexins biosynthesis and phytoanticipins in vegetables. The interest in genistein has increased due to its pharmacological effects, including anti-cancer activity, neuroprotective effects, cardiovascular protection, anti-inflammatory effects, antioxidant activity, and prevention of obesity. The most challenging issue for improving genistein is its low oral bioavailability, which has led to many animal and human pharmacokinetic studies and numerous clinical trials. Several drug delivery systems have been developed to protect and stabilize genistein to overcome the challenge of low bioavailability. This work concerns a revision of the literature reporting nano and microformulations for genistein encapsulation, including lipid nanoparticles, liposomes, tocotrienol-rich nanoemulsions, polymeric nanoparticles, dextran complexes, chitosan complexes, and Fe3O4 nanoparticles with carboxymethylated chitosan. Regarding the enormous potential of genistein, several clinical trials and marketed formulations can be found in the market.


Asunto(s)
Quitosano , Neoplasias , Animales , Humanos , Genisteína/farmacología , Genisteína/uso terapéutico , Quitosano/uso terapéutico , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Nanotecnología
19.
J. Phys. Educ. (Maringá) ; 34: e3458, 2023. tab, graf
Artículo en Portugués | LILACS | ID: biblio-1550463

RESUMEN

RESUMO O trabalho em questão, tem como objetivo central apresentar uma pesquisa voltada às principais motivações relacionadas à prática de atividades físicas durante o período de graduação no curso de Psicologia na Universidade Federal de Mato Grosso do Sul (UFMS). Desse modo, o instrumento utilizado será um questionário realizado e formulado pelos alunos pesquisadores, assim, pretende-se analisar o principal interesse precursor da prática, sendo as opções: diversão, hobby, descontração, competência, autoestima, saúde física ou influência social, além do levantamento da frequência da atividade realizada. Além disso, como fator secundário, procura-se perceber as razões daqueles que não realizam nenhum tipo de atividade, tendo como questões de escolha: motivos financeiros, falta de tempo, escolha própria e falta de motivação por parte da universidade. O questionário irá aborda ainda se os entrevistados pretendem iniciar alguma prática futuramente. Com base nos resultados, será possível deduzir a importância da prática de atividades físicas e principalmente seus benefícios, que se enquadram na melhora inclusive do desempenho acadêmico, e associar tais questões com os motivos dos não- praticantes também.


ABSTRACT The main objective of this work is to present a research focused on the main motivations related to the practice of physical activities during the graduation period in the Psychology course at the Federal University of Mato Grosso do Sul (UFMS). In this way, the instrument used will be a questionnaire carried out and formulated by the research students, thus, it is intended to analyze through this, the main precursor interest of the practice, being the options: fun, hobby, relaxation, competence, self-esteem, physical health or by social influence, and the frequency of the activity carried out. In addition, as a secondary factor, an attempt is made to understand the reasons of those who do not carry out any type of activity, having as choice issues: financial reasons, lack of time, own choice and lack of motivation on the part of the university, and as an additional, ask if they intend to start some practice in the future. Based on the results, it is possible to deduce the importance of the practice of physical activities and mainly its benefits, which fit in the improvement sometimes, even, of the academic performance, and to associate such questions with the motives of the non-practitioners as well.


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Psicología/educación , Estudiantes , Ejercicio Físico/fisiología , Educación y Entrenamiento Físico , Rendimiento Académico
20.
Estud. Psicol. (Campinas, Online) ; 40: e200210, 2023. tab
Artículo en Inglés | LILACS, INDEXPSI | ID: biblio-1448229

RESUMEN

Objective: Cancer illness is a stressful event that affects children's quality of life. This study verified the association between coping and quality of life in 13 children with cancer (6 to 12 years old) from a public hospital in the Southeastern region of the country. Methods: The participants answered the Hospitalization Coping Scale and Pediatric Quality of Life 3.0 (Cancer Module). Descriptive and inferential statistical analyses were applied. A high average of adaptive coping and coping behaviors, such as talking, playing, and taking medicine, were observed. Results: The results suggest a potential positive correlation between quality of life related to the domain nausea, which also showed high scores, and adaptive coping, demonstrating children's difficulty in dealing with nausea, even after using adaptive coping strategies, and this domain was significant in reducing the quality of life perceived. Conclusion: Understanding coping and qualitywww of life may steer intervention in Pediatric Oncology.


Objetivo: O adoecimento por câncer é um evento estressor que afeta a qualidade de vida das crianças. Este estudo verificou associações entre coping e qualidade de vida em 13 crianças com câncer (6 a 12 anos), atendidas em um hospital público da região sudeste do país. Método: Os participantes responderam a Escala de Coping da Hospitalização e Pediatric Quality of Life 3.0 (Cancer Module). Análises estatísticas descritivas e inferenciais foram aplicadas. Médias elevadas de coping adaptativo e de comportamentos de coping, como conversar, brincar e tomar remédio, foram verificadas. Resultados: Os resultados sugerem uma possível correlação positiva entre qualidade de vida relacionada ao domínio "enjoo", que também apresentou escores altos, e coping adaptativo, demonstrando a dificuldade das crianças para lidarem com náuseas, mesmo usando estratégias de coping adaptativo, sendo esse domínio significativo na diminuição da qualidade de vida percebida. Conclusão: Foi concluído que a compreensão do coping e da qualidade de vida pode direcionar a assistência psicológica em Oncologia Pediátrica.


Asunto(s)
Calidad de Vida , Adaptación Psicológica , Niño , Hospitalización , Neoplasias
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