Estimates of avoided costs attributed to a short cervix screening program to prevent preterm birth from the perspective of the Unified Health System (SUS)

OBJECTIVE: To perform an economic cost analysis of the implementation of a short cervix screening program to reduce preterm birth in singleton pregnancies in a short-term time horizon. METHODS: We performed a cost-benefit economic analysis using the P5 trial database, a randomized multicenter clinical trial for prevention of preterm birth. Data collection was conducted from July 2015 to March 2019 in 17 different Brazilian hospitals. We conducted a cost analysis for universal cervical screening in singleton pregnancies between 18 weeks and 22 weeks plus 6 days. In subjects with a cervical length ≤ 25 mm, the analysis incorporated the costs of administering 200 mg/day of vaginal progesterone prophylactically until 36 weeks gestation. These findings were subsequently compared with the economic implications of forgoing cervical screening. The time horizon comprised from birth to 10 weeks postpartum. The outcome was measured monetarily in Brazilian real (R$) from the perspective of the Unified Health System. RESULTS: Among 7,844 women, 6.67$ 383,711.36, while non-screening generated an estimated additional cost of R$446,501.69 (related to the 29 non-screened preterm deliveries). Thus, screening and prophylaxis would generate a final cost reduction of R$ 62,790.33, constituting a possible cost-benefit strategy. CONCLUSION: Universal short cervix screening for preterm birth has lower costs compared to non-screening within a short-term time horizon, which suggests an interesting benefitcost ratio. Future studies should consider the cost-effectiveness of prophylactic treatment using sensitivity analyses in different scenarios within the Brazilian health system, as well as analyses that consider the long-term costs associated with preterm births, to robustly justify the implementation of a short cervix screening program.OBJETIVO: Realizar uma análise econômica de custo da implementação de um programa de rastreio de colo curto para redução da prematuridade em gestações únicas num horizonte temporal de curto prazo. MÉTODOS: Realizamos uma análise econômica do tipo custo-benefício utilizando o banco de dados do P5 trial, um ensaio clínico multicêntrico randomizado para prevenção da prematuridade. A coleta de dados ocorreu de julho de 2015 a março de 2019 em 17 diferentes hospitais do Brasil. Comparamos os custos do rastreamento universal em mulheres com gestação única de 18 a 22 semanas e 6 dias associado à progesterona vaginal profilática 200 mg/dia até 36 semanas naquelas com colo ≤ 25 mm com os do não rastreamento. O horizonte temporal foi do nascimento até 10 semanas após o parto. O desfecho foi medido monetariamente em real brasileiro (R$) na perspectiva do Sistema Único de Saúde. RESULTADOS: Entre 7.844 mulheres, 6,67$ 383.711,36, enquanto o não rastreamento gerou custo adicional estimado de R$446.501,69 (relacionado aos 29 partos prematuros não rastreados). Assim, o rastreamento mais a profilaxia geraria uma redução de custo final de R$ 62.790,33, apresentando-se como uma possível estratégia de custo-benefício. CONCLUSÃO: O rastreamento universal de colo curto para prematuridade apresenta menores custos em relação ao não rastreamento dentro de um horizonte temporal de curto prazo, o que sugere uma interessante relação de custo versus benefício. Novos estudos que considerem a custo-efetividade do tratamento profilático utilizando-se de análises de sensibilidade em diferentes cenários dentro do sistema de saúde brasileiro, assim como análises que considerem os custos de longo prazo atrelados ao nascimento prematuro, são necessários para justificar com robustez a implementação de um programa de rastreamento

In Vitro Screening

This research was funded by Fundação para a Ciência e a Tecnologia (FCT-MCTES), Radiation Biology and the Biophysics Doctoral Training Programme (RaBBiT, PD/00193/2012); the scholarship grant number PD/BD/142829/2018, to T.P.P. from the RaBBiT Doctoral Training Programme. Publisher Copyright: © 2023 by the authors.Photodynamic therapy is a minimally invasive procedure used in the treatment of several diseases, including some types of cancer. It is based on photosensitizer molecules, which, in the presence of oxygen and light, lead to the formation of reactive oxygen species (ROS) and consequent cell death. The selection of the photosensitizer molecule is important for the therapy efficiency; therefore, many molecules such as dyes, natural products and metallic complexes have been investigated regarding their photosensitizing potential. In this work, the phototoxic potential of the DNA-intercalating molecules—the dyes methylene blue (MB), acridine orange (AO) and gentian violet (GV); the natural products curcumin (CUR), quercetin (QT) and epigallocatechin gallate (EGCG); and the chelating compounds neocuproine (NEO), 1,10-phenanthroline (PHE) and 2,2′-bipyridyl (BIPY)—were analyzed. The cytotoxicity of these chemicals was tested in vitro in non-cancer keratinocytes (HaCaT) and squamous cell carcinoma (MET1) cell lines. A phototoxicity assay and the detection of intracellular ROS were performed in MET1 cells. Results revealed that the IC50 values of the dyes and curcumin in MET1 cells were lower than 30 µM, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 µM. The IC50 of MB and AO was greatly affected by irradiation when submitted to 640 nm and 457 nm light sources, respectively. ROS detection was more evident for cells treated with AO at low concentrations. In studies with the melanoma cell line WM983b, cells were more resistant to MB and AO and presented slightly higher IC50 values, in line with the results of the phototoxicity assays. This study reveals that many molecules can act as photosensitizers, but the effect depends on the cell line and the concentration of the chemical. Finally, significant photosensitizing activity of acridine orange at low concentrations and moderate light doses was demonstrated.publishersversionpublishe

Characterization, physicochemical stability, and evaluation of in vitro digestibility of solid lipid microparticles produced with palm kernel oil and tristearin

Solid lipid particles have been investigated by food researchers due to their ability to enhance the incorporation and bioavailability of lipophilic bioactives in aqueous formulations. The objectives of this study were to evaluate the physicochemical stability and digestibility of lipid microparticles produced with tristearin and palm kernel oil. The motivation for conducting this study was the fact that mixing lipids can prevent the expulsion of the bioactive from the lipid core and enhance the digestibility of lipid structures. The lipid microparticles containing different palm kernel oil contents were stable after 60 days of storage according to the particle size and zeta potential data. Their calorimetric behavior indicated that they were composed of a very heterogeneous lipid matrix. Lipid microparticles were stable under various conditions of ionic strength, sugar concentration, temperature, and pH. Digestibility assays indicated no differences in the release of free fatty acids, which was approximately 30% in all analises. The in vitro digestibility tests showed that the amount of palm kernel in the particles did not affect the percentage of lipolysis, probably due to the high amount of surfactants used and/or the solid state of the microparticles.The authors are grateful to the FAPESP and CNPq for the scholarships granted (J.C.S., FAPESP fellowships 2010/13229-8 and 2012/02316-2, and T. R. B, FAPESP fellowship 2010/15031-0) and to Agropalma S/A for their generous palm kernel oil donation. Author Ana C. Pinheiro gratefully acknowledges the fellowship (SFRH/BD/48120/2008) granted by the Fundacao para a Ciencia e Tecnologia (FCT, Portugal)

Genetic analysis of enteropathogenic Escherichia coli (EPEC) adherence factor (EAF) plasmid reveals a new deletion within the EAF probe sequence among O119 typical EPEC strains

Enteropathogenic Escherichia coli (EPEC) are classified into typical and atypical strains based on the presence of the E. coli adherence factor (EAF) plasmid. The EAF plasmid contains the bfp (bundle-forming pilus) operon and the perABC (plasmid encoded regulator) gene cluster. A 1-kb cryptic region of EAF plasmid has been widely used as a genetic probe for EPEC detection. However, some EPEC strains may harbor an EAF plasmid lacking the EAF probe sequence, which makes the differentiation between typical and atypical a complex task. In this study, we report the genetic analysis of the EAF plasmid-encoded genes in a collection of EPEC clinical isolates. A total of 222 EPEC clinical isolates, which were previously classified as typical (n = 70) or atypical (n = 152) by EAF probe reactivity, were screened for the presence of different EAF sequences by PCR and DNA hybridization. All typical strains possessed intact bfpA and perA genes, and most of them were positive in the PCR for EAF probe sequence. However, a subset of 30 typical strains, 22 of which belonged to O119 serogroup, presented a 1652 pb deletion in the region between 1093-bp downstream perC and 616-bp of the EAF fragment. The bfpA, bfpG, and per genes were found in all typical strains. In addition, 32 (21 %) atypical strains presented the perA gene, and 20 (13.2 %) also presented the bfpA gene. Among the 32 strains, 16 belonged to the O119:H2, O119:HND, and ONT:HND serotypes. All 32 atypical strains contained perA mutation frameshifts and possessed an IS1294 element upstream of the per operon as detected by PCR followed by restriction fragment length polymorphism (RFLP) typing and multiplex PCR. Among the 20 bfpA probe-positive strains, eight O119 strains possessed deletion in the bfp operon at the 3'end of bfpA due to an IS66 element. Our data show that typical O119 strains may contain a deletion within the EAF probe sequence not previously reported. This new finding suggests that care should be taken when using the previously described EAF PCR assay in epidemiological studies for the detection of typical O119 strains. In addition, we were able to confirm that some atypical strains carry vestiges of the EAF plasmid.1520

Characterization of protective immune responses induced by pneumococcal surface protein A in fusion with Pneumolysin derivatives

Pneumococcal surface protein A (PspA) and Pneumolysin derivatives (Pds) are important vaccine candidates, which can confer protection in different models of pneumococcal infection. Furthermore, the combination of these two proteins was able to increase protection against pneumococcal sepsis in mice. The present study investigated the potential of hybrid proteins generated by genetic fusion of PspA fragments to Pds to increase cross-protection against fatal pneumococcal infection. Pneumolisoids were fused to the N-terminus of clade 1 or clade 2 pspA gene fragments. Mouse immunization with the fusion proteins induced high levels of antibodies against PspA and Pds, able to bind to intact pneumococci expressing a homologous PspA with the same intensity as antibodies to rPspA alone or the co-administered proteins. However, when antibody binding to pneumococci with heterologous PspAs was examined, antisera to the PspA-Pds fusion molecules showed stronger antibody binding and C3 deposition than antisera to co-administered proteins. In agreement with these results, antisera against the hybrid proteins were more effective in promoting the phagocytosis of bacteria bearing heterologous PspAs in vitro, leading to a significant reduction in the number of bacteria when compared to co-administered proteins. The respective antisera were also capable of neutralizing the lytic activity of Pneumolysin on sheep red blood cells. Finally, mice immunized with fusion proteins were protected against fatal challenge with pneumococcal strains expressing heterologous PspAs. Taken together, the results suggest that PspA-Pd fusion proteins comprise a promising vaccine strategy, able to increase the immune response mediated by cross-reactive antibodies and complement deposition to heterologous strains, and to confer protection against fatal challenge

Hearing health of workers exposed to noise and insecticides

OBJECTIVE: To examine the peripheral auditory disorders in a group of workers exposed to organophosphate and pyrethroid insecticides, used in vector control campaigns. METHODS: The prevalence study examined a population of 98 individuals who sprayed insecticides in campaigns for the prevention of Dengue, Chagas disease and Yellow fever. The sampling approach was finalistic, and included the workers in a health district of Pernambuco, during the year 2000. A questionnaire was used to collect data on occupational and non-occupational risks, safety measures utilized, family history of auditory problems and health symptoms. Previous noise exposure history was also investigated, since noise can be a confounding factor for hearing loss. Hearing sensitivity and middle ear function were assessed by pure tone audiometry. RESULTS: Among those exposed to insecticides, 63.8% demonstrated a hearing loss. For the group of workers exposed to both noise and insecticides, hearing loss was observed in 66.7% of the cases. The median exposure time necessary to detect high-frequency losses was 3.4 years for workers exposed to both agents and 7.3 years for workers exposed to insecticides only. Hearing thresholds were poorest among workers exposed to both agents. Auditory damage for those with combined exposures to the two factors was more severe than the hearing losses observed among those exposed only to insecticides. CONCLUSIONS: There is evidence that exposure to insecticides was associated with peripheral sensorioneural hearing loss and that noise exposure can potentiate the ototoxic effects of insecticides. It is necessary to evaluate this possible association through epidemiological studies.OBJETIVO: Avaliar as alterações auditivas periféricas em um grupo de trabalhadores exposto a inseticidas, organofosforados e piretróides, utilizados em campanhas de controle de vetores. MÉTODOS: Estudo de prevalência de uma população de 98 indivíduos que pulverizavam venenos nas campanhas de prevenção do dengue, da febre amarela e da doença de Chagas. A amostra foi de tipo finalística, considerando o universo dos trabalhadores de um distrito sanitário, em Pernambuco, no ano de 2000. Utilizou-se questionário contendo questões de identificação de riscos ocupacional e não ocupacional, medidas de segurança utilizadas, antecedentes de problemas auditivos e sintomas referidos. Foi investigada a historia pregressa de exposição ao ruído, por ser um fator de confusão para a perda auditiva. Todos os indivíduos foram avaliados pelo teste de audiometria tonal. RESULTADOS: Dos expostos apenas aos inseticidas, 63,8% apresentaram perda auditiva. Para o grupo com exposição concomitantemente aos inseticidas e ao ruído, a perda auditiva foi de 66,7%. O tempo mediano para o desenvolvimento de alterações auditivas nas freqüências médias altas, para as exposições combinadas de inseticidas e ruído, foi de 3,4 anos e para as exposições apenas aos inseticidas foi de 7,3 anos. A perda auditiva para as exposições concomitantes aos dois fatores foi de maior intensidade nessas freqüências, do que o observado na exposição apenas aos inseticidas. CONCLUSÕES: Há evidência de que a exposição aos inseticidas induz dano auditivo periférico e que o ruído é um fator que interage com os inseticidas, potencializando seus efeitos ototóxicos. Faz-se necessário avaliar essa possível associação através de estudos epidemiológicos de caráter analítico

Silent polymorphisms in the RYR1 gene do not\ud modify the phenotype of the p.4898 I>T\ud pathogenic mutation in central core disease:\ud a case report

Background: Central core disease is a congenital myopathy, characterized by presence of central core-like areas in\ud muscle fibers. Patients have mild or moderate weakness, hypotonia and motor developmental delay. The disease is\ud caused by mutations in the human ryanodine receptor gene (RYR1), which encodes a calcium-release channel.\ud Since the RYR1 gene is huge, containing 106 exons, mutation screening has been limited to three ‘hot spots’, with\ud particular attention to the C-terminal region. Recent next- generation sequencing methods are now identifying\ud multiple numbers of variants in patients, in which interpretation and phenotype prevision is difficult.\ud Case presentation: In a Brazilian Caucasian family, clinical, histopathological and molecular analysis identified a\ud new case of central core disease in a 48-year female. Sanger sequencing of the C-terminal region of the RYR1\ud gene identified two different missense mutations: c.14256 A > C polymorphism in exon 98 and c.14693 T > C in\ud exon 102, which have already been described as pathogenic. Trans-position of the 2 mutations was confirmed\ud because patient’s daughter, mother and sister carried only the exon 98’s mutation, a synonymous variant that was\ud subsequently found in the frequency of 013–0,05 of alleles. Further next generation sequencing study of the whole\ud RYR1 gene in the patient revealed the presence of additional 5 common silent polymorphisms in homozygosis and\ud 8 polymorphisms in heterozygosis.\ud Conclusions: Considering that patient’s relatives showed no pathologic phenotype, and the phenotype presented\ud by the patient is within the range observed in other central core disease patients with the same mutation, it was\ud concluded that the c.14256 A > C polymorphism alone is not responsible for disease, and the associated additional\ud silent polymorphisms are not acting as modifiers of the primary pathogenic mutation in the affected patient. The\ud case described above illustrates the present reality where new methods for wide genome screening are becoming\ud more accessible and able to identify a great variety of mutations and polymorphisms of unknown function in\ud patients and their families.Fundação de Amparo a Pesquisa do Estado de São Paulo - Centro de Pesquisa, Inovação e Difusão (FAPESP-CEPID)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-INCT)Associação Brasileira de Distrofia Muscular (ABDIM)CAPES-COFECU

Knowledge and attitude of parents or caretakers regarding transmissibility os caries disease

Dental caries is a transmissible infectious disease in which mutans streptococci are generally considered to be the main etiological agents. Although the transmissibility of dental caries is relatively well established in the literature, little is known whether information regarding this issue is correctly provided to the population. The present study aimed at evaluating, by means of a questionnaire, the knowledge and usual attitude of 640 parents and caretakers regarding the transmissibility of caries disease. Most interviewed adults did not know the concept of dental caries being an infectious and transmissible disease, and reported the habit of blowing and tasting food, sharing utensils and kissing the children on their mouth. 372 (58.1%) adults reported that their children had already been seen by a dentist, 264 (41.3%) answered that their children had never gone to a dentist, and 4 (0.6%) did not know. When the adults were asked whether their children had already had dental caries, 107 (16.7%) answered yes, 489 (76.4%) answered no, and 44 (6.9%) did not know. Taken together, these data reinforce the need to provide the population with some important information regarding the transmission of dental caries in order to facilitate a more comprehensive approach towards the prevention of the disease

Determination of fipronil in bovine plasma by solid-phase extraction and liquid chromatography with ultraviolet detection

A fast and efficient method has been developed and validated for the determination of fipronil in bovine plasma. Samples were subjected to solid-phase extraction (SPE) followed by reversed phase liquid chromatography (LC) separation, using acetonitrile/water (60:40 v/v) as the mobile phase with a flow rate of 1.0 mL/min and ultraviolet (UV) detection at 210 nm. Ethiprole was used as the internal standard (IS). The method was found to be linear over the range 5-500 ng/mL (r = 0.999). The limit of quantitation (LOQ) was validated at 5 ng/mL. The method was successfully applied to monitor plasma concentrations following subcutaneous administration of fipronil in cattle