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INTRODUCCIÓN: La rickettsiosis, enfermedad potencialmente mortal, es trasmitida por vectores como Rhipicephalus sanguineus, Dermacentor variabilis y D. andersonii, reservorios de Rickettsia rickettsii. En Baja California, México, es endémica, multifactorial, tiene alta letalidad, sus manifestaciones clínicas inespecíficas y ataque multisistémico dificultan el diagnóstico y tratamiento oportuno. OBJETIVO: Identificar los factores de riesgo asociados a la letalidad por rickettsiosis trasmitida por garrapatas en Mexicali, Baja California. PACIENTES Y MÉTODOS : Estudio observacional, analítico, transversal, retrospectivo, de 40 registros de pacientes con diagnóstico confirmado de rickettsiosis, periodo 2014 a 2018. Variables analizadas: sociodemográficas, clínicas, laboratorio clínico, evolución y desenlace. Se reportan frecuencias y medidas de asociación. RESULTADOS: 24 defunciones y 16 vivos. Más de 90% tuvo contacto conocido con garrapatas. Afectó en su mayoría a < 45 años en ambos grupos. La evolución antes del ingreso fue similar y la estancia hospitalaria fue mayor en los pacientes vivos (3,2 ± 4.7 vs 10,62 ± 7,6 p = 0,0002). Fiebre, cefalea, mialgias fueron predominantes. Datos asociados con letalidad: disfunción respiratoria (OR 38,33 IC95% 4,06-361,3 p < 0,0001), creatinina elevada (OR 15,4 IC95% 3,08-76,77 p < 0,0003), retardo del llenado capilar (OR 13,0 IC95% 2,73-61,78 p = 0,0005), dolor abdominal (OR 8,33, IC95% 1,90-36,44 p = 0,0029), AST (OR 7,5, IC95% 1,69-33,27 p = 0,005). CONCLUSIÓN: Esta enfermedad requiere de identificación temprana de factores que se asocian con letalidad para un tratamiento oportuno y adecuado.
BACKGROUND: Rickettsiosis, a potentially fatal disease, is transmitted by vectors such as Rhipicephalus sanguineus, Dermacentor variabilis and D. andersonii, reservoirs of Rickettsia rickettsii. In Baja California, Mexico, it is endemic, multifactorial, has high lethality, its nonspecific clinical manifestations and multisystem attack make diagnosis and timely treatment difficult. AIM: Identify the risk factors associated with lethality due to tick-transmitted rickettsiosis in Mexicali, Baja California. METHODS: Observational, analytical, cross-sectional, retrospective study of 40 records of patients with a confirmed diagnosis of rickettsiosis, period 2014 to 2018. Analyzed variables: sociodemographic, clinical, clinical laboratory, evolution and outcome. Frequencies and association measures are reported. RESULTS: 24 patients died and 16 survived. More than 90% had reported contact with ticks. It mostly affected ≤ 45 years in both groups. The evolution before admission was similar, and the hospital stay was longer in patients who lived (3.2 ± 4.7 vs 10.62 ± 7.6 p = 0.0002). Fever, headache, and myalgia are predominant. Data associated with lethality: respiratory dysfunction (OR 38.33 95% CI 4.06-361.3 p < 0.0001), elevated creatinine (OR 15.4 95% CI 3.08-76.77 p < 0.0003), delayed capillary refill (OR 13.0, 95% CI 2.73-61.78 p = 0.0005), abdominal pain (OR 8.33, 95% CI 1.90-36.44 p = 0.0029), AST (OR 7.5, 95% CI 1.69-33.27 p = 0.005). CONCLUSION: This disease requires early identification of factors that are associated with lethality for timely and adequate treatment.
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Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Rickettsia Infections/mortality , Tick-Borne Diseases/mortality , Rickettsia , Rickettsia Infections/drug therapy , Cross-Sectional Studies , Risk Factors , Tick-Borne Diseases/drug therapy , Spotted Fever Group Rickettsiosis , Mexico/epidemiology , Anti-Bacterial Agents/therapeutic useРеферат
ABSTRACT Background: We evaluated the predictive factors for case confirmation and death from Brazilian spotted fever in an endemic area of Southeastern Brazil. Methods: A cross-sectional study was conducted. All suspected cases reported between 2007 and 2021 were analyzed using two logistic regression models. Results: 60 cases were confirmed. Male sex, age group of 40-59 years, tick parasitism, presence of capybaras or horses, exanthema and hospitalization were positively associated with confirmation. Death was associated with a longer period between first symptom-hospitalization and shorter treatment. Conclusions: Complete clinical evaluation and information on risk exposure are key to early suspicion, diagnosis, treatment and prevention of deaths.
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Resumen Introducción : Existe poca información sobre la pre sencia de COVID-19 en participantes de ensayos clínicos. El objetivo del estudio fue evaluar la tasa de infección acumulada por SARS-CoV-2 en esta población. Además, investigamos el riesgo, letalidad y mortalidad por CO VID-19. Métodos : Diseño observacional retrospectivo que incluyó adultos participantes en ensayos clínicos de intervención aprobados por nuestro comité de ética du rante los dos primeros años de la pandemia (31/3/2020 a 31/3/2022). Se excluyeron protocolos pediátricos, obser vacionales, de corta duración y con sujetos internados. Resultados : Se incluyeron 513 sujetos adultos que participaron en ensayos clínicos durante ese período de la pandemia por COVID-19. Los pacientes con CO VID-19 se caracterizaron por tener una edad de 59.7 ± 13.7 años (50% sexo femenino) y el 92% presentó riesgo incrementado de letalidad por COVID-19. La tasa acu mulada de COVID-19 fue de 9.74% (IC 95%: 7.32-12.64%) que se situó por debajo del 17% de la población de 60 a 69 años de la Argentina (p<0.0001). La tasa de letalidad por COVID-19 fue de 14% (IC 95%: 5.8-26.7), que se situó por encima del 2.45% de la población de 50 a 69 años de la Argentina (p<0.0001). Conclusión : La tasa de COVID-19 en los sujetos adultos participantes de ensayos clínicos estuvo por debajo de las cifras de la población argentina de simi lar edad. La tasa de letalidad estuvo por encima de las cifras poblacionales y se explica por el alto riesgo de esa población.
Abstract Introduction : There is little information on the pres ence of COVID-19 in clinical trial participants. The objec tive of the study was to evaluate the cumulative infec tion rate for SARS-CoV-2 in this population. Additionally, we investigated the risk, lethality, and mortality from COVID-19. Methods : The design was observational retrospective that included adult subjects participating in clinical intervention trials approved by our ethics committee during the first two years of the pandemic (March 31, 2020 to March 31, 2022). Pediatric, observational, short-term, and inpatient protocols were excluded. Results : We included 513 adult subjects who par ticipated in clinical trials during the first two years of the COVID-19 pandemic. Patients with COVID-19 were characterized as being 59.7 ± 13.7 years old (50% fe male), and 92% had an increased risk of fatality from COVID-19. The cumulative rate of COVID-19 was 9.74% (95% CI: 7.32-12.64%) and its confidence intervals were below 17% of the population aged 60 to 69 in Argentina (p<0.0001). The case fatality rate for COVID-19 was 14% (95% CI: 5.8%-26.7%) and its confidence intervals were above 2.45% of the population aged 50 to 69 in Argentina (p< 0.0001). Conclusion : The rate of COVID-19 in adult subjects participating in clinical trials was below the figures for the Argentine population of similar age. The fatality rate was above the population figures, and it is explained by the high risk of the population.
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Background and objective: the acquired immunodeficiency syndrome (AIDS) has high rates of detection and death in the state of Rio Grande do Sul. In order to better understand such deaths, in December 2017, the Uruguaiana Municipal Department of Health implemented the AIDS Mortality Committee (CMaids). This study aimed to analyze the impact of an CMaids implementation in Uruguaiana through municipal health indicators. Methods: an ecological time-series study that used secondary data from the official platforms of the Ministry of Health from 2008 to 2020. Results: a reduction in the indicators number of deaths (from 28 in 2008 to 9 in 2020), mortality rate (from 22.0 in 2008 to 7.1 deaths/100,000 inhabitants in 2020), and fatality rate (from 46.74 in 2008 to 9.61 deaths/1,000 inhabitants in 2020) was observed. Moreover, trend lines were verified between 2017-2020 through the logarithmic regression model with join points. A relevant Annual Percent Change in mortality and fatality indicators was verified, with a reduction of 59.1% and 73.4%, respectively, in 2020, when comparing the observed and expected values. Conclusion: the findings enable us to conjecture that CMaids contributed to health indicator improvement, evidencing this as a relevant strategy to handle HIV/AIDS endemic at the local level.(AU)
Justificativa e objetivo: a síndrome da imunodeficiência adquirida (aids) apresenta elevadas taxas de detecção e óbito no estado do Rio Grande do Sul. A fim de compreender melhor tais óbitos, em dezembro de 2017, a Secretaria Municipal de Saúde de Uruguaiana implementou o Comitê de Mortalidade por aids (CMaids). O objetivo deste estudo é analisar o impacto da implantação do CMaids de Uruguaiana por meio de indicadores de saúde municipais. Métodos: estudo ecológico de série temporal, utilizando dados secundários das plataformas oficiais do Ministério da Saúde entre o período de 2008 a 2020. Resultados: observou-se redução dos indicadores número de óbitos (de 28 em 2008 para 9 em 2020), taxa de mortalidade (de 22,0 em 2008 para 7,1 óbitos/100.000 habitantes em 2020) e taxa de letalidade (de 46,74 em 2008 para 9,61 óbitos/1.000 habitantes em 2020). Ainda, verificaram-se linhas de tendência entre 2017-2020 por meio do modelo de regressão logarítmica com pontos de junção. Averiguou-se relevante mudança percentual anual nos indicadores de mortalidade e letalidade, com redução de 59,1% e 73,4%, respectivamente, em 2020, ao comparar-se o valor observado e o esperado. Conclusão: os achados permitem conjecturar que o CMaids contribuiu para melhorias dos indicadores de saúde, evidenciando essa como uma estratégia relevante para o enfrentamento do HIV/aids em nível local.(AU)
Justificación y objetivo: el síndrome de inmunodeficiencia adquirida (sida) presenta altas tasas de detección y muerte en el estado de Rio Grande do Sul. Para entender mejor esas muertes, en diciembre de 2017, la Secretaría Municipal de Salud de Uruguaiana implementó el Comité de Mortalidad por SIDA (CMaids). El objetivo de este estudio es analizar el impacto de la implementación del CMaids de Uruguaiana a través de los indicadores de salud municipales. Métodos: estudio ecológico de series temporales, utilizando datos secundarios de las plataformas oficiales del Ministerio de Salud desde 2008 hasta 2020. Resultados: se observó la reducción de los indicadores de número de óbitos (de 28 en 2008 a 9 en 2020), tasa de mortalidad (de 22,0 en 2008 a 7,1 muertes/100.000 habitantes en 2020) y tasa de letalidad (de 46,74 en 2008 a 9,61 muertes/1.000 habitantes en 2020). Además, se verificaron líneas de tendencia entre 2017-2020 a través del modelo de regresión logarítmica con puntos de unión. Se verificó un cambio porcentual anual relevante en los indicadores de mortalidad y letalidad, con una reducción de 59,1% y 73,4%, respectivamente, en 2020, al comparar los valores observados y esperados. Conclusión: los resultados permiten conjeturar que el CMaids contribuye a mejorar los indicadores de salud, evidenciando que es una estrategia relevante para la lucha contra el VIH/SIDA a nivel local.(AU)
Тема - темы
Humans , Health Status Indicators , Acquired Immunodeficiency Syndrome/mortality , HIV , Ecological StudiesРеферат
Introduction: COVID-19 unfolded differently in Pará and Rio Grande do Sul, Brazil, owing to distinct socioeconomic contexts. From 2020 to 2022, both states implemented diverse measures against the virus SARS-CoV-2, including vaccination and variant monitoring, tailored to their specific challenges. Understanding regional impacts on COVID-19 indicators is crucial for designing effective control strategies. Objective: to analyze the incidence, mortality, and lethality of COVID-19 in Pará and Rio Grande do Sul and the trends of these indicators from 2020 to 2022. Methods: ecological study with time series from public and official data available in the Health Secretariat of Pará and Rio Grande do Sul, including all cases and deaths by COVID-19 from February 2020 to December 2022. Lethality, mortality, and incidence rates were calculated. Prais-Winsten regression analysis was used, and trends were classified as stationary, increasing, or decreasing. Significant differences were considered when the p-value is <0.05. Results: when examining the lethality rates between the states of Para and Rio Grande do Sul, an observable trend emerged during the analyzed period. It became evident that the total lethality rate consistently remained higher in Para. Noteworthy peaks in lethality were mainly observed during the months of April 2020, May 2020, and March 2021. The incidence rates showed increasing trends during 2020, both in Pará with a daily percentage change (DPC) of 1.69% (p <0.05) and in Rio Grande do Sul with a DPC of 1.70% (p<0.05). In 2021, the incidence was decreasing (p <0.05) in both states, with a DPC of 0.60% in Pará and 0.64% in Rio Grande do Sul and continued this trend in Pará in 2022 (DPC of -0.50% p <0.05), becoming stationary in Rio Grande do Sul, with a non-significant p-value (p> 0.05).Conclusion: the positive impact of the vaccination program is reflected in the evolution of the pandemic. During the study period Rio Grande do Sul and Para exhibited a stationary incidence trend, emphasizing the need for continued monitoring of cases and morbidity across various age and demographic groups.
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Introduction: the progression of SARS-CoV-2 highlighted the Americas region for the number of COVID-19 cases and deaths. In Brazil, the Southeast region was one of the most affected, especially the state of Rio de Janeiro, due to its cosmopolitan characteristics.Objective: to analyze temporal variations in the incidence, mortality and lethality of COVID-19 in the state of Rio de Janeiro from January 2020 to December 2022.Methods: ecological time-series study with publicly available data on COVID-19 cases and deaths. Crude incidence, mortality, and fatality rates, and estimates of percent daily change (DPC) were analyzed using Prais-Winsten linear regression. With calculation of crude rates were performed using Microsoft Excel 2019, and DPC estimates were performed using STATA MP 17.0 software.Results: 2.5 million cases and 76 thousand COVID-19 deaths were confirmed in the state of Rio de Janeiro from 2020 to 2022, with lethality declining from 4.89% to 0.60%. The highest lethality occurred in May 2020 (11.59%), October 2021 (9.13%) and March 2022 (6.78%), showing a stationary trend. In 2020, incidence and mortality rates peaked in December (797.76 per 100,000 inhabitants) and May (43.96 per 100,000 inhabitants), respectively, followed by subsequent declines. Incidence trend was increasing in 2020 and stationary in 2022, while mortality decreased in 2021 and 2022 after stability in 2020.Conclusion: The incidence of COVID-19 peaked in 2020 and subsequently declined, suggesting partial transmission control. Mortality stabilized after 2020, indicating evolution in health care. Lethality showed a stationary trend, indicating an improvement in hospital capacity. The divergent behavior of the epidemiological indicators reflected the complex dynamics of the pandemic in the analyzed state. There were 790 thousand deaths from COVID-19 in the State of Rio de Janeiro in the period from 2020 to 2022.
Introdução: a progressão do SARS-CoV-2 destacou a região das Américas pelo número de casos e óbitos de COVID-19. No Brasil, a região Sudeste foi uma das mais afetadas, em especial o estado do Rio de Janeiro, devido suas características cosmopolitas.Objetivo: analisar as variações temporais da incidência, mortalidade e letalidade da COVID-19 no estado do Rio de Janeiro no período de janeiro de 2020 a dezembro de 2022.Método: estudo ecológico de séries temporais com dados de acesso público de casos e óbitos de COVID-19. Analisou-se as taxas brutas de incidência, mortalidade e letalidade, e estimativas das taxas de variação percentual diária (DPC) utilizando a regressão linear de Prais-Winsten. Para o cálculo das taxas brutas usou-se o aplicativo Microsoft Excel 2019, e na estimativa da DPC o software STATA MP 17.0.Resultados: foram confirmados 2,5 milhões de casos e 76 mil óbitos por COVID-19 no estado do Rio de Janeiro, no período de 2020 a 2022, com letalidade declinando de 4,89% para 0,60%. A maior letalidade ocorreu em maio de 2020 (11,59%), outubro de 2021 (9,13%) e março de 2022 (6,78%), com tendência estacionária no período. Em 2020, as taxas de incidência e mortalidade, atingiu pico em dezembro (797,76/100 mil hab.), com posterior declínio e em maio (43,96/100 mil hab.), também com posterior queda, respectivamente. A tendência de incidência foi crescente em 2020 e estacionária em 2022, a mortalidade decresceu em 2021 e 2022, após estabilidade em 2020.Conclusão: a incidência de COVID-19 atingiu pico em 2020 e decresceu posteriormente, sugerindo controle parcial da transmissão. A mortalidade se estabilizou após 2020, indicando evolução da assistência à saúde. A letalidade apresentou tendência estacionária no período, sinalizando melhoria da capacidade hospitalar. O comportamento divergente dos indicadores epidemiológicos refletiu a complexa dinâmica da pandemia no estado do Rio de Janeiro. Houve 790 mil óbitos por COVID-19 no Estado do Rio de Janeiro no período de 2020 a 2022.
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Abstract The World Health Organization is the global coordinating agency for the response to the COVID-19 pandemic. In March 2023, the WHO announced the end of the COVID-19 emergency phase. The end of the Public Health Emergency of International Concern does not mean that COVID-19 has ceased to be a health threat. The worldwide spread of the disease continues to be characterized as a pandemic. The significance of this decision is aimed at public health systems everywhere for countries to transition from emergency mode to management of COVID-19 along with other infectious diseases. The COVID-19 pandemic is not over. The population got tired of the virus, however, the virus did not get tired of the human population. Non-pharmacological preventive measures, vaccination and health education continue to be the arsenal we must control this disease today.
Resumo A Organização Mundial da Saúde é a agência coordenadora global para a resposta à pandemia da COVID-19. No mês de março de 2023 a OMS anunciou o fim da fase de emergência da COVID-19. O fim da Emergência de Saúde Pública de Importância Internacional não significa que a COVID-19 tenha deixado de ser uma ameaça à saúde. A propagação mundial da doença continua caracterizada como uma pandemia. O significado dessa decisão é direcionado aos sistemas de saúde pública em todos os locais para os países realizarem a transição do modo de emergência para o de manejo da COVID-19 juntamente com outras doenças infecciosas. A pandemia da COVID-19 não acabou. A população cansou do vírus, entretanto, o vírus não cansou da população humana. As medidas preventivas não farmacológicas, a vacinação e a educação em saúde continua sendo o arsenal que temos para controlar essa doença nos dias atuais.
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Introducción: los síndromes coronarios agudos representan la forma aguda de la cardiopatía isquémica. Esta constituye, en Cuba, la primera causa de muerte en los últimos años. La provincia de Matanzas muestra un comportamiento similar. Objetivo: evaluar las tendencias de morbilidad y letalidad de los pacientes con síndrome coronario agudo en un período de cinco años. Materiales y métodos: se realizó un estudio descriptivo retrospectivo de corte transversal, con 734 pacientes ingresados con síndrome coronario agudo en la Unidad de Cuidados Intensivos Emergentes del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas, entre enero de 2016 y diciembre de 2020. Se caracterizaron los pacientes según variables clínicas. Los datos se extrajeron de las historias clínicas. Se aplicó el test Chi cuadrado. Resultados: hubo una disminución progresiva y continua del total de pacientes con síndrome coronario agudo en los cinco años estudiados. Sobresalió el sexo masculino, con un 53,67 % (p < 0,02). El grupo etario más afectado fue el de 60 a 69 años. El síndrome coronario agudo sin elevación del segmento ST prevaleció en cuatro de los años analizados. Preponderó la instauración del tratamiento trombolítico en el 78,75 % de los pacientes con síndrome coronario agudo con elevación del ST. El total de fallecidos decreció en el período estudiado. Se demostró la importancia de la aplicación de la trombolisis. Conclusiones: en el quinquenio estudiado, disminuyó gradualmente el total de pacientes con diagnóstico de síndrome coronario agudo, y la letalidad por esta causa, en la Unidad de Cuidados Intensivos Emergentes del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas.
Introduction: acute coronary syndromes represent the acute form of ischemic heart disease. In Cuba, it is the first cause of death in recent years. The province of Matanzas shows similar behavior. Objective: to evaluate morbidity and lethality tendencies of the patients with acute coronary syndrome in a period of five years. Materials and methods: a descriptive, retrospective, cross-sectional study was carried out with 734 patients admitted with acute coronary syndrome in the Emergency Intensive Care Unit of the Clinical Surgical University Hospital Comandante Faustino Perez, of Matanzas, between January 2016 and December 2020. The patients were characterized according to clinical variables. The data were extracted from clinical records. The Chi-square test was applied. Results: there was a progressive and continuous decrease of the total of patients with acute coronary syndrome in the studied five years. Male gender stood up with 53.67% (p < 0, 02). The most affected age group was the 60-69 years one. The acute coronary syndrome without ST segment elevation prevailed in four of the analyzed years. The establishment of the thrombolytic treatment prevailed in 78.75% of the patients with ST segment elevated acute coronary syndrome. The total of deaths decreased in the studied period. The importance of thrombolysis application was demonstrated. Conclusions: the total of patients with diagnosis of acute coronary syndrome and lethality due to this cause gradually decreased in the studied five-year period in the Emergency Intensive Care Unit of the Clinical Surgical Hospital Comandante Faustino Perez Hernandez, of Matanzas.
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Genome-guided oncology refers to a new treatment concept that transcends histological classification and pathological ty-ping and uses drugs according to the genetic characteristics of tumors. New drug development technology and clinical trial design based on this concept provide new ideas for the clinical application of precision oncology. The multi-component and multi-target characteristics of Chinese medicine provide rich resources for the development of tumor-targeting drugs from natural products, and the design of the master protocol trial aiming at the characteristics of precision oncology supports the rapid clinical screening of effective tumor-targeting drugs. The emergence of the synthetic lethality strategy breaks through the bottleneck that the drug can only target the oncogene but cannot do anything to the tumor suppressor gene with the loss-of-function mutation in the past. With the rapid development of high-throughput sequencing technology, the cost of sequencing is also decreasing. For the development of tumor-targeting drugs, how to keep up with the update speed of target information is a difficult problem of concern. Based on the integration of innovative ideas and me-thods of precision oncology, network pharmacology, and synthetic lethality strategy on synthetic lethal interaction network of antitumor Chinese medicine compatibility formula design, and the combination of improvement of innovative clinical trial methods, such as master protocol trial, basket trial, and umbrella trial, unique advantages of Chinese medicine are expected to be exerted beyond the antibody-based drugs and small molecule-based drugs and corresponding targeted drugs are potentially developed for clinical application.
Тема - темы
Humans , Neoplasms/genetics , Medicine, Chinese Traditional , Precision Medicine/methods , Medical Oncology , Antineoplastic Agents/therapeutic useРеферат
Aurora kinase A (Aurora-A), a serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer, including lung cancer, colorectal cancer, and breast cancer. Alteration of Aurora-A impacts multiple cancer hallmarks, especially, immortalization, energy metabolism, immune escape and cell death resistance which are involved in cancer progression and resistance. This review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance, including chemoresistance (taxanes, cisplatin, cyclophosphamide), targeted therapy resistance (osimertinib, imatinib, sorafenib, etc.), endocrine therapy resistance (tamoxifen, fulvestrant) and radioresistance. Specifically, the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair, feedback activation bypass pathways, resistance to apoptosis, necroptosis and autophagy, metastasis, and stemness. Noticeably, our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1, ARID1A and MYC gene mutation tumors, and potential synergistic strategy for mTOR, PAK1, MDM2, MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A kinase. In addition, we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.
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During the tumorigenic process, cancer cells may become overly dependent on the activity of backup cellular pathways for their survival, representing vulnerabilities that could be exploited as therapeutic targets. Certain molecular vulnerabilities manifest as a synthetic lethality relationship, and the identification and characterization of new synthetic lethal interactions may pave the way for the development of new therapeutic approaches for human cancer. Our goal was to investigate a possible synthetic lethal interaction between a member of the Chromodomain Helicase DNA binding proteins family (CHD4) and a member of the histone methyltransferases family (SETDB1) in the molecular context of a cell line (Hs578T) representing the triple negative breast cancer (TNBC), a subtype of breast cancer lacking validated molecular targets for treatment. Therefore, we employed the CRISPR-Cas9 gene editing tool to individually or simultaneously introduce indels in the genomic loci corresponding to the catalytic domains of SETDB1 and CHD4 in the Hs578T cell line. Our main findings included: a) introduction of indels in exon 22 of SETDB1 sensitized Hs578T to the action of the genotoxic chemotherapy doxorubicin; b) by sequentially introducing indels in exon 22 of SETDB1 and exon 23 of CHD4 and tracking the percentage of the remaining wild-type sequences in the mixed cell populations generated, we obtained evidence of the existence of a synthetic lethality interaction between these genes. Considering the lack of molecular targets in TNBC, our findings provided valuable insights for development of new therapeutic approaches not only for TNBC but also for other cancer types.
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Background and objectives: understanding the social situation of COVID-19 in poor and less developed countries is still doubtful. Thus, this study aimed to estimate the incidence and lethality by COVID-19, according to the per capita income of the administrative regions of the Federal District (FD). Methods: this is a descriptive ecological study, based on secondary data. Thirty-one administrative regions of the FD were included, and the population consisted of 382,488 individuals. The variables considered were sex, incidence, mortality, lethality, age group, population estimate and education. Results: despite the greater contamination by women, in terms of total mortality, more men died, representing 57.3% of the total deaths in the period. Regarding the influence of the level of education and income on the incidence, it appears that the highest rates of confirmed cases occurred in groups with higher levels of education and income. Despite this higher incidence, it is the group that exhibits the lowest lethality and the third lowest mortality per 100,000 inhabitants. Conclusion: the highest incidence rates were observed in regions with higher per capita income. On the other hand, lethality occurred more incisively in regions with lower purchasing power. In view of this, it is necessary to apply long-term preventive measures in unequal regions.(AU)
Justificativa e objetivos: o entendimento da situação social da COVID-19 em países pobres e menos desenvolvidos ainda é dubitável. Desse modo, o objetivo deste estudo é estimar a incidência e letalidade por COVID-19, de acordo com a renda per capita das regiões administrativas do Distrito Federal (DF). Métodos: trata-se de um estudo ecológico descritivo, baseado em dados secundários. Foram incluídas 31 regiões administrativas do DF, e a população foi composta por 382.488 indivíduos. Consideraram-se como variáveis sexo, incidência, mortalidade, letalidade, faixa etária, estimativa populacional e escolaridade. Resultados: apesar da contaminação maior por parte das mulheres, em termos de mortalidade total, mais homens foram a óbito, representando 57,3% do total de mortos no período. A respeito da influência do grau de escolaridade e da renda na incidência, verifica-se que os maiores índices de casos confirmados aconteceram em grupos com maior nível de escolaridade e de renda. Apesar dessa maior incidência, é o grupo que exibe a menor letalidade e a terceira menor mortalidade por 100.000 habitantes. Conclusão: as mais altas taxas de incidência foram observadas nas regiões com maior renda per capita. Por outro lado, a letalidade ocorreu, de forma mais incisiva, nas regiões de menor poder aquisitivo. Diante disso, é necessário aplicar medidas preventivas de longo prazo em regiões desiguais.(AU)
Justificación y objetivos: la comprensión de la situación social del COVID-19 en los países pobres y menos desarrollados aún es dudosa. Así, el objetivo de este estudio es estimar la incidencia y letalidad por COVID-19, según el ingreso per cápita de las regiones administrativas del Distrito Federal (DF). Métodos: se trata de un estudio ecológico descriptivo, basado en datos secundarios. Se incluyeron 31 regiones administrativas del DF, la población estuvo conformada por 382,488 individuos. Se consideraron como variables el sexo, la incidencia, la mortalidad, la letalidad, el grupo de edad, la población estimada y la escolaridad. Resultados: a pesar de la mayor contaminación por mujeres, en términos de mortalidad total, fallecieron más hombres, representando el 57,3% del total de defunciones en el período. En cuanto a la influencia del nivel de educación e ingresos en la incidencia, parece que las tasas más altas de casos confirmados ocurrieron en grupos con mayores niveles de educación e ingresos. A pesar de esta mayor incidencia, es el grupo que presenta la menor letalidad y la tercera mortalidad más baja por 100.000 habitantes. Conclusión: las tasas de incidencia más altas se observaron en las regiones con mayor ingreso per cápita. Por otro lado, la letalidad se produjo de forma más incisiva en las regiones de menor poder adquisitivo. Ante esto, es necesario aplicar medidas preventivas a largo plazo en regiones desiguales.(AU)
Тема - темы
Humans , Mortality , COVID-19/epidemiology , Per Capita IncomeРеферат
Introducción: En Cuba el comportamiento de la epidemia de la COVID-19 ha sido analizado desde el enfoque de varias ciencias, con la guía de la Epidemiología, para frenar su expansión. Se requiere estudiar su comportamiento atendiendo al estado de la población para identificar sus diferenciales, lo cual puede ayudar en la adopción de medidas para su enfrentamiento. Objetivo: Evaluar la incidencia de la COVID-19 en Cuba a partir de indicadores sociodemográficos. Métodos: Se utilizaron los cálculos de las tasas de incidencia, mortalidad y la letalidad de la COVID-19 por grupos de edades y sexo a nivel de país y sus territorios. Se compararon estas tasas con indicadores demográficos seleccionados. Se utilizaron los datos aportados por diversos sitios oficiales del país en el periodo del 11 de marzo al 12 de junio de 2020. Resultados: La edad fue el principal diferencial de las tasas de mortalidad y la letalidad por COVID-19, con mayor frecuencia en los mayores de 60 años, fundamentalmente en hombres. No se evidenció ninguna variación proporcional entre dichas tasas y el grado de urbanización, la densidad poblacional y el grado de envejecimiento de la población. Conclusiones: Para disminuir el impacto de la COVID-19 en Cuba fueron decisivas las medidas adoptadas por el Gobierno, fundamentalmente las que estaban en función de los grupos más vulnerables. El estudio de los diferenciales de la COVID-19 desde la Demografía constituye un punto de partida para la búsqueda de factores de diversa naturaleza que influyen en su comportamiento(AU)
Introduction: In Cuba, the behavior of the COVID-19 epidemic has been analyzed from the approach of several sciences, with the guidance of Epidemiology, to stop its spread. It is necessary to study its behavior according to the state of the population to identify their differentials, which can help in the adoption of measures to confront them. Objective: Asses the incidence of COVID-19 in Cuba based on socio-demographic indicators. Methods: Calculations of COVID-19 incidence, mortality and lethality rates by age groups and sex were used at the country and territory levels. These rates were compared with selected demographic indicators. The data provided by various official sites of the country in the period from March 11 to June 12, 2020 were used. Results: Age was the main differential in mortality rates and lethality due to COVID-19, with greater frequency in those over 60 years of age, mainly in men. There was no evidence of any proportional variation between these rates and the degree of urbanization, population density and degree of population ageing. Conclusions: To reduce the impact of COVID-19 in Cuba, the measures adopted by the Government were decisive, mainly those that were based on the most vulnerable groups. The study of the differentials of COVID-19 from Demography constitutes a starting point for the search of different nature factors that influence its behavior(AU)
Тема - темы
Humans , Male , Female , COVID-19/mortality , COVID-19/epidemiology , Sociodemographic Factors , CubaРеферат
Introduction: continual mutations of the sars-cov-2 virus, with the possibility of reinfection or reactivation of the virus, can lead to a further spread of the virus and consequently new infection periods. The state of pernambuco, brazil, has faced many adversities amidst the pandemic, requiring studies and new spatiotemporal techniques to understand the pandemic development and planning actions to reverse the current situation.Objective: the aim was to evaluate the mortality and lethality trends of covid-19 from april 2020 to june 2021 in the state of pernambuco, brazil, with the division into two periods according to the waves of infection to date (1st period and 2nd period).Methods: an ecological time-series study was carried out with population data from the pernambuco state health department. We collected the number of confirmed cases and deaths for covid-19. The trends were analyzed according to the prais-winsten regression model in two moments from march 2020 to september 2020 and the second from october 2021 to june 2022. Differences were considered significant when p<0.05.Results: the state of pernambuco had 581,594 confirmed cases of covid-19, where 51,370 were severe cases, and 530,224 were mild cases, in addition to 18,444 deaths. Given the trends analyzed, mortality was increasing in the second period (april/2020 to june/2021), while lethality decreased in the first period and was stationary in the second period.Conclusion: this study found an increasing trend in mortality of covid-19 in the state of pernambuco, brazil in the second period, highlighting an urgent need to develop surveillance measures as well as public policies for vulnerable populations, in addition to continuing preventive measures.
Introdução: mutações contínuas do vírus SARS-CoV-2, com possibilidade de reinfecção ou reativação do vírus, podem levar a uma maior disseminação do vírus e, consequentemente, novos períodos de infecção. O estado de Pernambuco, Brasil, tem enfrentado muitas adversidades em meio à pandemia, exigindo estudos e novas técnicas espaço-temporais para entender o desenvolvimento da pandemia e planejar ações para reverter a situação atual.Objetivo: o objetivo foi avaliar as tendências de mortalidade e letalidade do COVID-19 de abril de 2020 a junho de 2021 no estado de Pernambuco, Brasil, com a divisão em dois períodos de acordo com as ondas de infecção até o momento (1º Período e 2º Período).Método: foi realizado um estudo ecológico de série temporal com dados populacionais da Secretaria Estadual de Saúde de Pernambuco. Coletamos o número de casos confirmados e óbitos por COVID-19. As tendências foram analisadas segundo o modelo de regressão Prais-Winsten em dois momentos de março de 2020 a setembro de 2020 e o segundo de outubro de 2021 a junho de 2022. As diferenças foram consideradas significativas quando p<0,05.Resultados: o estado de Pernambuco teve 581.594 casos confirmados de COVID-19, sendo 51.370 graves casos, sendo 530.224 casos leves, além de 18.444 óbitos. Dadas as tendências analisadas, a mortalidade foi crescente no segundo período (abril/2020 a junho/2021), enquanto a letalidade diminuiu no primeiro período e ficou estacionária no segundo período.Conclusão: este estudo encontrou uma tendência crescente na mortalidade por COVID-19 no estado de Pernambuco, Brasil no segundo período, destacando a necessidade urgente de desenvolver medidas de vigilância e políticas públicas para populações vulneráveis, além de continuar com as medidas preventivas adotadas até o momento.
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Introduction: In 2019, the proliferation of a virus identified as SARS-CoV-2 emerged in the city of Wuhan, a district in China, quickly spread throughout the world, gaining pandemic status and less than 1 year, its repercussions and magnitude caused scientists, governments and society to adopt severe measures to combat this disease. Objective: To analyze mortality, incidence and mortality from COVID-19 in the municipalities of Botucatu and Serrana, São Paulo, Brazil. Methods: This is an ecological study with a time series design with secondary data. All registered cases and deaths registered by COVID-19 from April 2020 to August 2021 in the municipalities of Botucatu and Serrana, São Paulo, Brazil were considered. The incidence, mortality and lethality rate were used. The monthly and/or weekly percentage variation and their respective 95% confidence intervals were estimated.Results: It identified that 12.88% of the residents of the city of Botucatu were infected with COVID-19 and 8.61% of the population of the municipality of Serrana was infected. There was a stationary trend of mortality and incidence in the period between April 2020 and May 2021 and decreasing in both sexes in the mortality rate in the municipality of Serrana, in the city of Botucatu there was a trend of increasing mortality and incidence in the same period observed. Conclusion: The mass vaccination strategy of citizens in the cities of Botucatu and Serrana present robust data to consider that immunization has a decreasing effect on the number of cases and deaths from COVID-19, which effectively contributes to fighting the pandemic and reduces the contamination and progression of the disease to more severe cases.
Introdução: em 2019, surgiu na cidade de Wuhan, um distrito na região da China a proliferação com a infecção de um vírus identificado como SARS-CoV-2, rapidamente espalhou-se pelo mundo ganhando status de pandemia em menos de 1 ano, suas repercussões e magnitude fizeram que os cientistas, governos e sociedade adotarem medidas severas para o combate a esta enfermidade. Objetivo: analisar a mortalidade, incidência e letalidade por COVID-19 nos municípios de Botucatu e Serrana, São Paulo, Brasil. Método: trata-se de um estudo ecológico com delineamento de série temporal com dados secundários. Foram consideradas todos os casos registrados e óbitos registrados por COVID-19 no período de abril de 2020 a agosto de 2021, nos municípios de Botucatu e Serrana, São Paulo, Brasil. Foi utilizado a taxa de incidência, mortalidade e letalidade. Estimou-se a variação percentual mensal e/ou semanal e seus respectivos intervalos de 95% de confiança. Resultados: identificou que e 12,88% dos munícipes da cidade de Botucatu foram infectados com COVID-19 e 8,61% da população do município de Serrana foi infectada. Observou-se uma tendência estacionária de mortalidade e incidência no período entre abril 2020 a maio 2021 e decrescente em ambos os sexos na taxa de letalidade no município de Serrana, na cidade de Botucatu houve tendência de mortalidade e incidência crescentes no mesmo período observado. Conclusão: a estratégia de vacinação em massa dos munícipes das cidades de Botucatu e Serrana apresentam dados robustos para considerar que a imunização tem efeito de queda no número de casos e óbitos por COVID-19, o que contribui efetivamente no combate a pandemia e reduz a contaminação e evolução da doença para casos mais graves.
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The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 continues to have a major impact on health and social systems around the world. The COVID-19 and influenza manifest themselves in a similar way, causing respiratory diseases that can present asymptomatically, as well as from the cold to severe respiratory problems until death. The form of transmission is similar, through contact with droplets or particles of saliva and secretions, which implies preventive actions that involve the same hygiene measures, use of masks and the need to cough using the elbow or disposable tissues. This characterizes a syndemic. It becomes necessary to monitor these diseases so that there are parameters for better decision-making on the appropriate clinical management of these respective diseases.
A pandemia de COVID-19 causada pelo novo coronavírus SARS-CoV-2 continua a ter um grande im-pacto nos sistemas de saúde e sociais em todo o mundo. torna-se necessário que haja monitoramento dessas doenças para que assim, tenha-se parâmetros para melhor tomada de decisão sobre a gestão clínica adequada sobre essas respectivas doenças. Os dois vírus se manifestam de forma semelhante, ao causarem doenças respiratórias que podem se apresentar de forma assintomáticas, assim como do resfriado a problemas respiratórios graves até a morte. A forma de transmissão são parecidas, por contato com gotículas ou partículas de saliva e secreções, o que implica nas ações de prevenção que perpassam pelas mesmas medidas higienização, uso de máscaras e a necessidade de tossir usando o cotovelo ou lenções descartáveis. Isto caracteriza uma sindemia.
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Poly ADP⁃ribose polymerase 1 (PARP1) is an important modification enzyme in cells. Its most well⁃known function is to recruit multiple DNA damage repair effector proteins through its own PARylation, such as XRCC1, to participate in DNA single and double strand damage repair. In addition, PARP1 can also provide favorable conditions for DNA damage repair and maintain genomic stability by promoting replication fork stall and nucleosome depolymerization. In recent years, in addition to the function of DNA damage repair, PARP1 has also been found to play an important role in cell apoptosis, autophagy and inflammatory pathways, which is closely related to the occurrence and development of neurodegenerative diseases. PARP inhibitor (PARPi) is an antitumor drug that targets PARP1 and works together with a homologous recombination (HR) deficient phenotype to produce a synthetic lethality. The drug can trap PARP1 and inhibit its activity. On the one hand, it directly interferes with the DNA damage repair pathway that PARP1 participates in; and on the other hand, it also inhibits the selection of PARP1⁃mediated DNA damage repair pathway and replication fork stall, making the cell genome instable. However, tumor cells are often found to be insensitive to PARPi in clinical treatment. Drug resistance of tumor cells to PARPi is highly correlated with mutations of their own genes, which respectively act on cell HR repair pathway, PARP1 circulation pathway, replication fork stability and active drug efflux, etc. Identifying specific mutation sites in drug⁃resistant tumor cells will provide help for clinical treatment. The purpose of this review is to give a description about the functions of PARP1, and focus on the mechanism of action of PARPi, the mutated genes related to drug resistance and their drug resistance mechanism, therefore to deepen the understanding of PARP1 mediated DNA damage repair pathway in cells, and provide new ideas for future clinical treatment.
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ABSTRACT Human Visceral Leishmaniasis (HVL) presents a subacute clinical evolution with systemic involvement, which can result in high case fatality, especially among untreated individuals or those with low socioeconomic status. This study aimed to identify epidemiological and clinical factors associated with HVL case fatality in the Ceara State, from 2007 to 2018. This is an analytical cross-sectional study. The bivariate analysis was performed by Stata 15.1 using Pearson's Chi-square or Fisher's exact test; and Poisson regression for age-controlled multivariate analysis. From 2007 to 2018, there were 4,863 new confirmed cases and 343 deaths from HVL (case fatality rate=7.05%). The risk factors associated with case fatalities were: age group (RR=8.69; 95%CI:3.56-21.20); black population (RR=2.21; 95%CI:1.45-3.35); jaundice symptoms (RR=1.72; 95%CI:1.38-2.14); edema (RR=2.62; 95%CI:2.10-3.26) and hemorrhagic phenomena (RR=1.63; 95%CI:1.26-2.10); and no prescription drug intake (RR=4.03; 95%CI:2.98-5.46). Treatment with pentavalent antimonial was a protective factor (RR=0.35; 95%CI:0.27-0.45). The number of deaths increased among the elderly, illiterate, urban residents, and black skin color individuals. The drugs pentavalent antimonial and amphotericin B showed an association with death, but were not considered causal factors. Treatment failure led to a high risk of death. In multivariate analysis, the risk factors for fatal cases were age group, black skin, symptoms of jaundice, edema and hemorrhagic phenomena; and failure to take the prescription drugs. Treatment with pentavalent antimonial was shown to be a protective factor. Knowing the factors associated with the fatality of VL-HIV cases may help to improve public policies, in order to refine the epidemiological surveillance program and, consequently, prevent deaths related to the disease in Ceara.
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ABSTRACT Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a growing threat to public health. Methods: A 3-year retrospective study was conducted to evaluate the prevalence and lethality of multidrug-resistant (MDR) A. baumannii isolated from Brazilian patients. Results: In this study, 219 Acinetobacter baumannii isolates were identified, of which 70.8% (155/219) were isolated from patients hospitalized in intensive care units. Of these, 57.4% (n = 89/155) were assessed, of which 92.1% (82/89) were carbapenem-resistant, and 49 were classified as infected. The lethality rate was 79.6% (39/49). Conclusions: We highlight the need of an effective epidemiological surveillance measure to contain the dissemination of CRAB in the hospital environment.
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The first confirmed case of COVID-19 was notified to the Brazilian Ministry of Health on February 26, 2020. On November 20, 2021, by the end of Epidemiological Week-46 (EW-46) 257,168,692 confirmed cases of COVID-19 reported worldwide. Among the countries with the highest number of accumulated cases the United States of America ranks number one (47,701,872), followed by India (34,510,413), Brazil (22,012,150), the United Kingdom (9,857,658), and Russia (9,135,149). Concerning deaths, 5,146,467 were confirmed worldwide until November 20, 2021. The United States was the country with the highest accumulated number of deaths (771,013), followed by Brazil (612,587), India (465,662), Mexico (292,145), and Russia (257,891).
O primeiro caso confirmado de COVID-19 foi notificado ao Ministério da Saúde (MS) do Brasil em 26 de fevereiro de 2020. Até o final da Semana Epidemiológica (SE) 46 de 2021, no dia 20 de novembro de 2021, foram confirmados 257.168.692 casos de covid-19 no mundo. Os Estados Unidos foram o país com o maior número de casos acumulados (47.701.872), seguido pela Índia (34.510.413), Brasil (22.012.150), Reino Unido (9.857.658) e Rússia (9.135.149). Em relação aos óbitos, foram confirmados 5.146.467 no mundo até o dia 20 de novembro de 2021. Os Estados Unidos foram o país com maior número acumulado de óbitos (771.013), seguido do Brasil (612.587), Índia (465.662), México (292.145) e Rússia (257.891)