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Cervical cancer constitutes a significant health burden for women worldwide despite being preventable by vaccination and screening. Advanced stages of the disease are associated with a poor prognosis, and treatment approaches have seen little change over several decades, resulting in an overall survival rate of no more than 17 months. Additionally, there are limited options for second-line treatment. The urgent need for innovative and effective therapies to improve the outlook for this group of patients, along with an enhanced understanding of the interactions between the disease and the host's immune system, has propelled immunotherapy into a rapidly advancing field with notable achievements. Among various immunotherapeutic approaches, immune checkpoint inhibitors emerge as the most advanced treatment option. Clinical trials assessing these inhibitors as single agents or in combination with chemotherapy show promising results. As immunotherapy begins to redefine standards of care for metastatic, recurrent, or persistent cervical cancer, this review addresses recent advances and current recommendations for its management in both first and second-line treatment. The goal is to provide insights into the evolving landscape of cervical cancer treatment, specifically focusing on immunotherapeutic interventions.
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Cervical cancer (CC) remains among the most frequent cancers worldwide despite advances in screening and the development of vaccines against human papillomavirus (HPV), involved in virtually all cases of CC. In mid-income countries, a substantial proportion of the cases are diagnosed in advanced stages, and around 40% of them are diagnosed in women under 49 years, just below the global median age. This suggests that members of this age group share common risk factors, such as chronic inflammation. In this work, we studied samples from 46 patients below 45 years old, searching for a miRNA profile regulating cancer pathways. We found 615 differentially expressed miRNAs between tumor samples and healthy tissues. Through bioinformatic analysis, we found that several of them targeted elements of the JAK/STAT pathway and other inflammation-related pathways. We validated the interactions of miR-30a and miR-34c with JAK1 and STAT3, respectively, through dual-luciferase and expression assays in cervical carcinoma-derived cell lines. Finally, through knockdown experiments, we observed that these miRNAs decreased viability and promoted proliferation in HeLa cells. This work contributes to understanding the mechanisms through which HPV regulates inflammation, in addition to its canonical oncogenic function, and brings attention to the JAK/STAT signaling pathway as a possible diagnostic marker for CC patients younger than 45 years. To our knowledge to date, there has been no previous description of a panel of miRNAs or even ncRNAs in young women with locally advanced cervical cancer.
Assuntos
Regulação Neoplásica da Expressão Gênica , Inflamação , MicroRNAs , Fator de Transcrição STAT3 , Transdução de Sinais , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/genética , Adulto , Inflamação/genética , Inflamação/patologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Células HeLa , Janus Quinase 1/metabolismo , Janus Quinase 1/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In Mexico, this pioneering research was undertaken to assess the accessibility of timely diagnosis of Dyads [Children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) and their primary caregivers] at specialized mental health services. The study was conducted in two phases. The first phase involved designing an "Access Pathway" aimed to identify barriers and facilitators for ADHD diagnosis; several barriers, with only the teacher being identified as a facilitator. In the second phase, the study aimed to determine the time taken for dyads, to obtain a timely diagnosis at each stage of the Access Pathway. As well as identify any disparities based on gender and socioeconomic factors that might affect the age at which children can access a timely diagnosis. METHOD: In a retrospective cohort study, 177 dyads participated. To collect data, the Acceda Survey was used, based on the robust Conceptual Model Levesque, 2013. The survey consisted of 48 questions that were both dichotomous and polytomous allowing the creation of an Access Pathway that included five stages: the age of perception, the age of search, the age of first contact with a mental health professional, the age of arrival at the host hospital, and the age of diagnosis. The data was meticulously analyzed using a comprehensive descriptive approach and a nonparametric multivariate approach by sex, followed by post-hoc Mann-Whitney's U tests. Demographic factors were evaluated using univariable and multivariable Cox regression analyses. RESULTS: 71% of dyads experienced a late, significantly late, or highly late diagnosis of ADHD. Girls were detected one year later than boys. Both boys and girls took a year to seek specialized mental health care and an additional year to receive a formal specialized diagnosis. Children with more siblings had longer delays in diagnosis, while caregivers with formal employment were found to help obtain timely diagnoses. CONCLUSIONS: Our findings suggest starting the Access Pathway where signs and symptoms of ADHD are detected, particularly at school, to prevent children from suffering consequences. Mental health school-based service models have been successfully tested in other latitudes, making them a viable option to shorten the time to obtain a timely diagnosis.
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Transtorno do Deficit de Atenção com Hiperatividade , Diagnóstico Precoce , Acessibilidade aos Serviços de Saúde , Serviços de Saúde Mental , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Masculino , Feminino , México/epidemiologia , Adolescente , Estudos Retrospectivos , Serviços de Saúde Mental/estatística & dados numéricos , Fatores SocioeconômicosRESUMO
Background: The aim of the present study was to describe the presence of co-infection by Toxoplasma gondii and Neospora caninum in goats reared in extensive systems from Mexico. Materials and Methods: A cross-sectional study was conducted to determine the frequency of T. gondii and N. caninum, by detecting antibodies to each parasite by mean commercial ELISA kits. A total of 176 blood samples were randomly collected from mature females reared in extensive system herds from 20 municipalities of state of Guanajuato, Mexico. Results: The general seroprevalence was 23.9 and 21.0% for T. gondii and N. caninum, respectively, while co-infection rate was 3.6%. For geographic and environmental variables, no differences were observed among T. gondii and coinfection; however, it was observed that altitude, annual precipitation, annual average temperature, and rainy period showed significant differences with N. caninum seropositive goats. Conclusion: The seroprevalence of both parasites was appreciated in most of the studied herds. The present study is the first report of T. gondii and N. caninum co-infection in goats from extensive herds in Mexico.
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Coccidiose , Coinfecção , Doenças das Cabras , Cabras , Neospora , Toxoplasma , Toxoplasmose Animal , Animais , Coccidiose/veterinária , Coccidiose/epidemiologia , Coccidiose/parasitologia , México/epidemiologia , Toxoplasma/imunologia , Doenças das Cabras/epidemiologia , Doenças das Cabras/parasitologia , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/parasitologia , Coinfecção/epidemiologia , Coinfecção/veterinária , Coinfecção/parasitologia , Estudos Soroepidemiológicos , Feminino , Estudos Transversais , Anticorpos Antiprotozoários/sangueRESUMO
Despite the universal vaccination program, there are still regions and territories with a high prevalence of Hepatitis B Virus infection (HBV), such as the Amazon basin, where several indigenous communities live. Additionally, Hepatitis Delta Virus (HDV) is a defective that requires the hepatitis B surface antigen (HBsAg) for the assembly and release of de novo viral particles. Therefore, hepatitis D could be the result of HBV/HDV coinfection or HDV superinfection in individuals with chronic hepatitis B. Among the high prevalence HDV populations are indigenous communities of America. This study aims to describe and characterize the frequency of HBV and HDV infection, viral genotypes and HBV immune escape mutants in indigenous populations from different regions of Colombia. The diagnosis of hepatitis B and hepatitis D was confirmed by serological markers. Moreover, the HBV and HDV genome were amplified by PCR and RT-PCR, respectively, and, subsequently, the phylogenetic analysis was performed. We characterized 47 cases of chronic hepatitis B, 1 case of reactivation and 2 cases of occult hepatitis B infection (OBI). Furthermore, a high prevalence of HDV infection was identified in the study population (29.33%, 22/75) and the circulation of several HBV genotypes and subgenotypes (F1b, F3, F4, and D). Interestingly, this is the first report of the HDV genotype I circulation in this country. These findings demonstrated that HBV and HDV infections are still public health problems in indigenous communities in Colombia.
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The general assumption that the survival patterns of tropical and southern temperate birds are similar lacks empirical data from higher latitudes. Regional comparisons of New World species are rare, and this assumption has been based on data from African studies. Here, we estimate the survival rates of 88 tropical and southern temperate bird populations (69 species) from eight localities in South America to evaluate the hypothesis that the survival of these populations is homogeneous at the regional scale. We estimated survival based on the Cormack-Jolly-Seber model and compared values from different environments. The survival estimates ranged from 0.30 to 0.80 (0.56 ± 0.12). Apparent survival did not differ significantly between low-latitude tropical environments (03°S) and the other sites from high-latitudes (between 22° and 34°S). Despite a predicted positive trend, body size was not significantly related to survival among passerines. On the other hand, phylogenetic relationships explained more than a third of the variation in bird survival. Based on the largest available database on South American bird species, our findings support the hypothesis that bird survival is homogeneous, at the regional scale, along the southern hemisphere. In particular, we reinforce the hypothesis that climatic variation has a limited influence on bird survival in the southern hemisphere.
Assuntos
Clima Tropical , Filogenia , América do Sul , Tamanho CorporalRESUMO
The quality of wine grapes and wine depends on their content of phenolic compounds. Under commercial conditions, the phenolic maturity of grapes is mostly achieved by applying abscisic acid analogues. Some Ca forms represent a cost-effective alternative for these compounds. In this study, 'Shiraz' vines (veraison of 90%) were sprayed with CaCO3-rich residues from the cement industry (4.26 g of Ca per L). Fruit from treated and untreated vines was harvested 45 days after CaCO3 spraying and evaluated for quality. The fruit was vinified, and the obtained wines were bottled and stored in darkness for 15 months at 20 °C. Wines were evaluated for quality after storage. The evaluation of grape and wine quality included the content of phenolic compounds and antioxidant capacity. The treatment with CaCO3 did not affect the ripening rate of grapes. However, the treatment improved the fruit yield as well as the color development, the content of phenolic compounds, and antioxidant capacity of grapes and wine. The treatment favored especially the accumulation of malvidin-3-O-glucoside, pelargonidin-3-O-glucoside, caftaric acid, caffeic acid, trans-cinnamic acid, quercetin, catechin, epicatechin, resveratrol, and the procyanidins B1 and B2. Wine made with treated fruit was of higher quality than that of control fruit.
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PURPOSE: The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis. METHODS: This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up. RESULTS: The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution ( P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%). CONCLUSIONS: Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes.
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Endoftalmite , Ceratite , Humanos , Vitrectomia/métodos , Ceratoplastia Penetrante/métodos , México/epidemiologia , Resultado do Tratamento , Endoftalmite/diagnóstico , Endoftalmite/cirurgia , Endoftalmite/tratamento farmacológico , Ceratite/cirurgia , Estudos RetrospectivosRESUMO
The mechanisms of ecological segregation involved in the coexistence between Neotropical felids are the key to support strategies for conservation. Due to their inconspicuous and elusive behavior, camera trapping constitute a strategic, non-invasive method to study these species. The present work aimed to evaluate the daily and seasonal activity patterns of four felid species: Leopardus guttulus (Hensel, 1872), L. pardalis (Linnaeus, 1758), L. wiedii (Schinz, 1821) and Puma concolor (Linnaeus, 1771), in the Papagaios-de-Altitude Private Protected Area, state of Santa Catarina, southern Brazil. Data were collected from January 2018 to December 2019, using 25 sites of camera traps among the study area. We collected 624 independent records from L. guttulus (108), L. pardalis (55), L. wiedii (77) and P. concolor (384) in a sampling effort of 12,266 camera-traps/day. All species analysed showed a non-uniform distribution of daily activity, when considering the two years. We report the peak of seasonal activity for all species between the months of June and September, coinciding with the Araucaria nut harvest in the study area, and with the increase in populations of small rodents. We also report a high overlap between the activity patterns of the four species. The daily and seasonal activity patterns of the species in this study seem to reflect the intrinsic dynamics of the Araucaria Forest, as well as possible adaptations to prey availability.(AU)
Os mecanismos de segregação ecológica envolvidos na coexistência entre felídeos neotropicais são a chave para subsidiar estratégias para sua conservação. Por apresentarem comportamento inconspícuo e esquivo, as armadilhas fotográficas constituem um método não invasivo estratégico para estudá-los. O presente trabalho buscou avaliar o padrão de atividade diário e sazonal de quatro espécies de felídeos: Leopardus guttulus (Hensel, 1872), L. pardalis (Linnaeus, 1758), L. wiedii (Schinz, 1821) e Puma concolor (Linnaeus, 1771), na RPPN Papagaios-de-Altitude, no estado de Santa Catarina, sul do Brasil. Coletamos os dados através de 25 sítios de armadilhas fotográficas na área de estudo. Obtivemos 624 registros independentes de L. guttulus (108), L. pardalis (55), L. wiedii (77) e P. concolor (384) em um esforço amostral de 12.266 armadilhas/dia. Todas as espécies analisadas apresentaram distribuição de atividade diária não uniforme, quando considerados os dois anos. Relatamos o pico de atividade sazonal de todas as espécies entre os meses de junho a setembro, coincidindo com a safra de pinhão na região, e com o aumento nas populações de pequenos roedores. Também relatamos uma alta sobreposição entre os padrões de atividade das quatro espécies. A atividade diária e sazonal das espécies neste estudo parece refletir as dinâmicas intrínsecas da Floresta Ombrófila Mista, além de possíveis adaptações à disponibilidade de presas.(AU)
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Felidae , Distribuição Animal , Brasil , Ritmo CircadianoRESUMO
Even though the site index is a popular method for describing forest productivity, its use is limited in uneven-aged multispecies forests. Accordingly, the site form (SF) is an alternative measure of productivity to the site index based on the tree height-diameter relationship. Our study aims to evaluate SF as a measure of productivity in the temperate uneven-aged multispecies forests of Durango, Mexico, applying three methods to estimate SF: (i) as the mean height of dominant trees at a reference diameter (SFH-D); (ii) as the expected mean height of dominant trees at a reference mean diameter (SFMH-MD), and (iii) as the expected height at a reference diameter for a given site (SFh-dbh). We assess the effectiveness of the SF based on two hypotheses: (i) the SF correlates to the total volume production, and (ii) the SF is independent of stand density. The SFH-D and the SFh-dbh showed a high correlation with productivity. However, they also did so with density. Contrary to this, the SFMH-MD had a weak correlation with density and productivity. We conclude that the SF is a suitable approach to describe site quality. Nonetheless, its effectiveness as a site quality indicator may be affected according to the method used.