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BACKGROUND: Cervical cancer eradication is one of the main goals for 2030 by the World Health Organization, which can only be achieved with high vaccination rates against Human Papilloma Virus. In Colombia, more and better scientific evidence is required to increase confidence in vaccination. The objective of this study is to evaluate the safety profile of the quadrivalent vaccine against HPV in the risk of developing autoimmune, neurological, and hematological diseases in adolescent women in Colombia. METHODS: We designed a cohort study based on national HPV vaccination records and incident diagnostic data for the diseases of special interest during 2012 and 2021. We included adolescent women between 9 and 19 years old and compared vaccinated and non-vaccinated cohorts using an Inverse Probability of Treatment Weighting (IPWT) method for each scenario disease and follow-up period (180 and 360 days). FINDINGS: The Odds Ratio (OR) of developing diseases of interest was estimated during two follow up periods, 180 and 360 days after the follow-up index date (Vaccination Day). The OR for developing rheumatoid arthritis was 4·4; CI95% (1·74 - 11·14), juvenile idiopathic arthritis was 2·76 IC95% (1·50 - 5·11), idiopathic thrombocytopenic purpura was 2·54 IC95% (1·28 - 5·02) and thyrotoxicosis was 2·86 IC95% (1·03 - 7·95), when comparing the vaccinated versus unvaccinated population. However, the temporal distribution of cases incident did not reveal a clear difference between the cohorts, since the rate of appearance of new cases has a constant linear behavior for the two groups. INTERPRETATION: For rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic thrombocytopenic purpura, and thyrotoxicosis; the application of the vaccine had an effect on the development of the disease. Nevertheless, our results should be interpreted with caution and be further studied, considering that the biological plausibility of the events occurred without a clear temporal pattern in relation to the exposure to the vaccine.
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Artrite Juvenil , Artrite Reumatoide , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Púrpura Trombocitopênica Idiopática , Tireotoxicose , Neoplasias do Colo do Útero , Adolescente , Criança , Feminino , Humanos , Adulto Jovem , Estudos de Coortes , Colômbia/epidemiologia , Papillomavirus Humano , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/efeitos adversos , Vacinação/métodos , Vacinas CombinadasRESUMO
BACKGROUND: Cervical cancer (CC) is globally ranked fourth in terms of incidence and mortality among women. Vaccination against Human Papillomavirus (HPV) and screening programs can significantly reduce CC mortality rates. Hence, executing cost-effective public health policies for prevention and surveillance is crucial. However, defining policies that make the best use of the available resources is not easy, as it requires predicting the long-term costs and results of interventions on a changing population. Since the simpler task of predicting the results of public health policies is difficult, devising those that make the best usage of available resources is an arduous challenge for decision-makers. METHODS: This paper proposes a fine-grained epidemiological simulation model based on differential equations, to effectively predict the costs and effectiveness of CC public health policies that include vaccination and screening. The model represents population dynamics, HPV transmission within the population, likelihood of infection clearance, virus-induced appearance of precancerous lesions and eventually CC, as well as immunity gained with vaccination and early detection with screening. RESULTS: We offer a compartmentalized modeling approach that separates population, epidemics, and intervention concerns. We instantiate models with actual data from a Colombian case study and analyze their results to show how our modeling approach can support CEA studies. Moreover, we implement models in an open-source software tool to simultaneously define and evaluate multiple policies. With the support of the tool, we analyze 54 policies within a 30-year time horizon and use as a comparator the CC policy that has been used until recently. We identify 8 dominant policies, the best one with an ICER of 6.3 million COP (Colombian Pesos) per averted DALY. We also validate the modeling approach against the available population and HPV epidemic data. The effects of uncertainty in the values of key parameters (discount rate, sensitivity of screening tests) is evaluated through one-way sensitivity analysis. CONCLUSIONS: Our modeling approach can provide valuable support for healthcare decision-makers. The implementation into an automated tool allows customizing the analysis with country-specific data, flexibly defining public health policies to be evaluated, and conducting disaggregate analyses of their cost and effectiveness.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Análise Custo-Benefício , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Colômbia/epidemiologia , Vacinação , Política Pública , Papillomavirus Humano , Política de Saúde , Vacinas contra Papillomavirus/uso terapêuticoRESUMO
Microalgae provides an alternative for the valorization of industrial by-products, in which the nutritional content varies substantially and directly affects microalgae system performance. Herein, the heterotrophic cultivation of Chlorella sorokiniana was systematically studied, allowing us to detect a nutritional deficiency other than the carbon source through assessing the oxygen transfer rate for glucose or acetate fermentation. Consequently, a mathematical model of the iron co-limiting effect on heterotrophic microalgae was developed by exploring its ability to regulate the specific growth rate and yield. For instance, higher values of the specific growth rate (0.17 h-1) compared with those reported for the heterotrophic culture of Chlorella were obtained due to iron supplementation. Therefore, anaerobic sludge from an industrial wastewater treatment plant (a baker's yeast company) was pretreated to obtain an extract as a media supplement for C. sorokiniana. According to the proposed model, the sludge extract allowed us to supplement iron values close to the growth activation concentration (KFe ~12 mg L-1). Therefore, a fed-batch strategy was evaluated on nitrogen-deprived cultures supplemented with the sludge extract to promote biomass formation and fatty acid synthesis. Our findings reveal that nitrogen and iron in sludge extract can supplement heterotrophic cultures of Chlorella and provide an alternative for the valorization of industrial anaerobic sludge.
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BACKGROUND: The present investigation evaluated 4 different solvent compositions for their relative capacity to extract total phenolic and total flavonoid (TF) components of the leaves, trunks, and stems of Bucida buceras L. (Combretaceae), and the stems of Phoradendron californicum (Viscaceae), plus mesquite and oak species endemic to the Southwestern United States, northern Mexico, and tropical regions of Central and South America, as well as to profile the composition of these plant materials and to measure their antioxidant capacity. METHODS: The total phenolic content of plant material used in the present investigation was measured using the Folin-Ciocalteau assay. Total flavonoids were assayed by AlCl3 and 2,4-dinitrophenylhydrazin colorimetry. Nitroblue tetrazolium was utilized for scavenging of superoxide anion, and in vitro antioxidant activity was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl and Ferric Reducing/Antioxidant Power assays. RESULTS: Phytochemical screening of each plant extract evaluated revealed the following major results: (1) No evidence of alkaloids for each of the extraction phases tested was detected in the hexanic, ethanolic, or aqueous phases of Bucida buceras and Phoradendron californicum (oak and mesquite); (2) Analysis of the hexane phase of B. buceras and P. californicum (mesquite) extracts revealed the presence of carotenes, triterpenes/steroids, and lactonic groups; (3) Analysis of the ethanol and aqueous extraction phases for both plants revealed the presence of a diverse range of compounds, including tripterpenes/steroids, lactonics groups, saponins, phenols/tannins, amines and/or amino acids, and flavonoids/anthocyanins; and (4) The highest total phenolic and flavonoid content were observed in P. californicum (oak): 523.886 ± 51.457 µg GAE/mg extract and 409.651 ± 23.091 µg/mg of extract for methanol and aqueous fractions, respectively. The highest flavonoid content was 237.273 ± 21.250 µg PNE/mg extract in the acetone extract of Bucida buceras stems; while the flavonol content (260.685 ± 23.031 µg CE/mg extract) was higher in the ethanol extract of P. californicum (oak). The acetone extract of B. buceras trunk extract showed the highest levels of DPPH radical-scavenging activity (IC50 = 4.136 ± 0.446 µg/mL) and reducing power (4928.392 ± 281.427 µM AAE/mg extract). The highest superoxide radical scavenging activity (IC50) was 55.249 ± 9.829 µg/mL, observed in acetone extracts of B. buceras leaves. CONCLUSIONS: The results of the present investigation demonstrated the effects of extraction solvent on phenolic and flavonoid content yield-and antioxidant activities by Bucida buceras and Phoradendron californicum. The present investigation further revealed that Bucida buceras exhibited optimal antioxidant capacity when acetone was used as extraction solvent; and the highest yield of phenols and flavonoids were obtained from the P. californicum oak, using methanol and aqueous solvents, respectively.
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Antioxidantes/farmacologia , Combretaceae/química , Extratos Vegetais/química , Solventes/química , Viscaceae/química , Flavonoides/análise , Fenóis/análise , Estruturas Vegetais/químicaRESUMO
BACKGROUND: Reactive Oxygen Species (ROS) impair the physiological functions of Retinal Pigment Epithelial (RPE) cells, which are known as one major cause of age-related macular degeneration and retinopathy diseases. The purpose of this study is to explore the cytoprotective effects of the antioxidant Bucida buceras extract in co-treatment with hydrogen peroxide (H2O2) delivery as a single addition or with continuous generation using glucose oxidase (GOx) in ARPE-19 cell cultures. The mechanism of Bucida buceras extract is believed to be associated with their antioxidant capacity to protect cells against oxidative stress. METHODS: A comparative oxidative stress H2O2-induced was performed by addition and enzymatic generation using glucose oxidase on human retinal pigment epithelial cells line. H2O2-induced injury was measured by toxic effects (cell death and apoptotic pathway) and intracellular redox status: glutathione (GSH), antioxidant enzymes (catalase and glutathione peroxidase) and reducing power (FRAP). The retino-protective effect of co-treatment with Bucida buceras extract on H2O2-induced human RPE cell injury was investigated by cell death (MTT assay) and oxidative stress biomarkers (H2O2, GSH, CAT, GPx and FRAP). RESULTS: Bucida buceras L. extract is believed to be associated with the ability to prevent cellular oxidative stress. When added as a pulse, H2O2 is rapidly depleted and the cytotoxicity analyses show that cells can tolerate short exposure to high peroxide doses delivered as a pulse but are susceptible to lower chronic doses. Co-treatment with Bucida buceras was able to protect the cells against H2O2-induced injury. In addition to preventing cell death treatment with antioxidant plant could also reverse the significant decrease in GSH level, catalase activity and reducing power caused by H2O2. CONCLUSION: These findings suggest that Bucida buceras could protect RPE against ocular pathogenesis associated with oxidative stress induced by H2O2-delivered by addition and enzymatic generation.
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Antioxidantes , Combretaceae/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais , Epitélio Pigmentado da Retina/citologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Humanos , Peróxido de Hidrogênio/toxicidade , Oxirredutases/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
PURPOSE: The prognostic value of hyperlactatemia in septic shock is unquestionable. However, as current definitions do not include hyperlactatemia as a mandatory criterion, some hypotensive patients may be diagnosed as having septic shock despite exhibiting normolactatemia. The significance of persistent sepsis-induced hypotension without hyperlactatemia is unclear. Is it really septic shock? Our aim was to determine differences in outcome between patients diagnosed as having septic shock but exhibiting normal vs elevated lactate levels during evolution. We also explored the potential implications of including hyperlactatemia as an obligatory diagnostic criterion. METHODS: We performed retrospective analyses on a cohort of 302 septic shock patients. RESULTS: When we divided patients according to the presence of hyperlactatemia, 34% evolved without hyperlactatemia and exhibited a very low mortality risk (7.7% compared with 42.9% of those with hyperlactatemia). These patients also presented less severe organ dysfunctions and higher central venous O(2) saturation values, and required lower norepinephrine doses. The potential inclusion of hyperlactatemia in septic shock definition would reduce incidence in 34% but increase absolute mortality risk in 11%. CONCLUSIONS: Persistent sepsis-induced hypotension without hyperlactatemia may not constitute a real septic shock. Our results support the need to review the current definition of septic shock. Hyperlactatemia could represent an objective parameter worth to be explored as a potential diagnostic criterion for septic shock.