RESUMO
Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms 'cfDNA', 'ctDNA', 'liquid biopsy' AND 'cancer OR neoplasm' in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients.
Assuntos
Biomarcadores Tumorais/análise , Ácidos Nucleicos Livres/análise , Ácidos Nucleicos Livres/metabolismo , Ensaios Clínicos como Assunto/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Animais , Ácidos Nucleicos Livres/genética , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Medicina de PrecisãoRESUMO
We propose a taxonomic revision of the dixenous trypanosomatids currently classified as Endotrypanum and Leishmania, including parasites that do not fall within the subgenera L. (Leishmania) and L. (Viannia) related to human leishmaniasis or L. (Sauroleishmania) formed by leishmanias of lizards: L. colombiensis, L. equatorensis, L. herreri, L. hertigi, L. deanei, L. enriettii and L. martiniquensis. The comparison of these species with newly characterized isolates from sloths, porcupines and phlebotomines from central and South America unveiled new genera and subgenera supported by past (RNA PolII gene) and present (V7V8 SSU rRNA, Hsp70 and gGAPDH) phylogenetic analyses of the organisms. The genus Endotrypanum is restricted to Central and South America, comprising isolates from sloths and transmitted by phlebotomines that sporadically infect humans. This genus is the closest to the new genus Porcisia proposed to accommodate the Neotropical porcupine parasites originally described as L. hertigi and L. deanei. A new subgenus Leishmania (Mundinia) is created for the L. enriettii complex that includes L. martiniquensis. The new genus Zelonia harbours trypanosomatids from Neotropical hemipterans placed at the edge of the Leishmania-Endotrypanum-Porcisia clade. Finally, attention is drawn to the status of L. siamensis and L. australiensis as nomem nudums.
Assuntos
Leishmania/genética , Filogenia , Trypanosomatina/classificação , Animais , América Central/epidemiologia , Genes de Protozoários , Humanos , Leishmaniose/epidemiologia , Leishmaniose/parasitologia , Leishmaniose/transmissão , Lagartos/parasitologia , Tipagem Molecular , Porcos-Espinhos/parasitologia , Psychodidae/parasitologia , RNA Ribossômico/genética , Bichos-Preguiça/parasitologia , América do Sul/epidemiologia , Trypanosomatina/genéticaRESUMO
Oriental melon (Cucumis melo L. var. makuwa) is an important fruit for human consumption. However, this plant species is one of the most recalcitrant to genetic transformation. The lack of an efficient in vitro system limits the development of a reproducible genetic transformation protocol for Oriental melon. In this study, an efficient transgenic production method for Agrobacterium-mediated transformation using cotyledon explants of Oriental melon was developed. Cotyledon explants were pre-cultivated for two days in the dark, and the optimal conditions for transformation of melon were determined to be a bacteria concentration of OD600 0.6, inoculation for 30 min, and two days of co-cultivation. Transgenic melon plants were produced from kanamycin-resistant shoots. A total of 11 independent transgenic plants were regenerated with a transformation efficiency of 0.8% of the inoculated explants. The transgenic plants were phenotypically normal and fully fertile, which might be a consequence of the co-cultivation time.
Assuntos
Agrobacterium tumefaciens/genética , Cucurbitaceae/genética , Plantas Geneticamente Modificadas/genética , Transformação Genética , Cotilédone , Cucurbitaceae/crescimento & desenvolvimento , Humanos , Plantas Geneticamente Modificadas/crescimento & desenvolvimentoRESUMO
Vaccination of domestic pets is an important component of rabies control and prevention in countries where the disease is maintained in a wildlife reservoir. In Grenada, vaccine coverage rates were low, despite extensive public education and advertising of government-sponsored vaccine clinics where rabies vaccine is administered to animals at no cost to animal owners. Information was needed on reasons for decreased dog owner participation in government-funded rabies vaccination clinics. A total of 120 dog owners from 6 different parishes were asked to complete a questionnaire assessing their currently held beliefs about rabies vaccination and perception of the risk posed by rabies. Over 70% of respondents believed that problems in the organization and management of clinic sites could allow for fighting between dogs or disease spread among dogs, while 35% of owners did not believe that they had the ability or adequate help to bring their dogs to the clinic sites. Recommendations for improving vaccine coverage rates included: improved scheduling of clinic sites and dates; increased biosecurity at clinic locations; focused advertising on the availability of home visits, particularly for aggressive dogs or dogs with visible skin-related diseases such as mange; and the recruitment of community volunteers to assist with bringing dogs to the clinic sites.
Assuntos
Doenças do Cão/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Raiva/veterinária , Vacinação/psicologia , Adolescente , Adulto , Idoso , Animais , Cães , Feminino , Granada , Humanos , Masculino , Pessoa de Meia-Idade , Raiva/prevenção & controle , Inquéritos e Questionários , Vacinação/veterinária , Adulto JovemRESUMO
AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death. METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22). CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.
Assuntos
Glicemia/análise , Doenças Cardiovasculares/epidemiologia , Transtornos do Metabolismo de Glucose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Ásia/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/epidemiologia , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/diagnóstico , Transtornos do Metabolismo de Glucose/mortalidade , Teste de Tolerância a Glucose , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , América do Sul/epidemiologia , Fatores de Tempo , Regulação para CimaRESUMO
AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death.METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22).CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.
Assuntos
Epidemiologia , Glucose , Infarto do MiocárdioRESUMO
We describe the distribution and abundance of the brain-encysting trematode Euhaplorchis californiensis and its second intermediate host, the California killifish (Fundulus parvipinnis), in 3 estuaries in southern California and Baja California. We quantified the density of fish and metacercariae at 13-14 sites per estuary and dissected 375 killifish. Density (numbers and biomass) was examined at 3 spatial scales, i.e., small replicate sites, habitats, and entire estuaries. At those same scales, factors that might influence metacercaria prevalence, abundance, and aggregation in host individuals and populations were also examined. Metacercaria prevalence was 94-100% among the estuaries. Most fish were infected with 100s to 1,000s of E. californiensis metacercariae, with mean abundance generally increasing with host size. Although body condition of fish did not vary among sites or estuaries, the abundance of metacercariae varied significantly among sites, habitats, estuaries, and substantially with host size and gender. Metacercariae were modestly aggregated in killifish (k > 1), with aggregation decreasing in larger hosts. Across the 3 estuaries, the total populations of killifish ranged from 9,000-12,000 individuals/ha and from 7-43 kg/ha. The component populations of E. californiensis metacercariae ranged from 78-200 million individuals/ha and from 0.1-0.3 kg/ha. Biomass of E. californiensis metacercariae constituted 0.5-1.7% of the killifish biomass in the estuaries. Our findings, in conjunction with previously documented effects of E. californiensis, suggest a strong influence of this parasite on the size, distribution, biomass, and abundance of its killifish host.
Assuntos
Encéfalo/parasitologia , Ecossistema , Doenças dos Peixes/parasitologia , Fundulidae/parasitologia , Trematódeos/fisiologia , Infecções por Trematódeos/veterinária , Animais , Biomassa , Encefalopatias/parasitologia , Encefalopatias/veterinária , California/epidemiologia , Feminino , Doenças dos Peixes/epidemiologia , Modelos Lineares , Modelos Logísticos , Masculino , México/epidemiologia , Prevalência , Caramujos , Trematódeos/crescimento & desenvolvimento , Infecções por Trematódeos/epidemiologia , Infecções por Trematódeos/parasitologiaRESUMO
We characterized four Brazilian trypanosomes isolated from domestic rats and three from captive non-human primates that were morphologically similar to T. lewisi, a considered non-pathogenic species restricted to rodents and transmitted by fleas, despite its potential pathogenicity for infants. These isolates were identified as T. lewisi by barcoding using V7V8 SSU rDNA sequences. In inferred phylogenetic trees, all isolates clustered tightly with reference T. lewisi and T. lewisi-like trypanosomes from Europe, Asia and Africa and despite their high sequence conservation formed a homogeneous clade separate from other species of the subgenus T. (Herpetosoma). With the aim of clearly resolving the relationships between the Brazilian isolates from domestic rats and primates, we compared sequences from more polymorphic ITS rDNA. Results corroborated that isolates from Brazilian rats and monkeys were indeed of the same species and quite close to T. lewisi isolates of humans and rats from different geographical regions. Morphology of the monkey isolates and their behaviour in culture and in experimentally infected rats were also compatible with T. lewisi. However, infection with T. lewisi is rare among monkeys. We have examined more than 200 free-ranging and 160 captive monkeys and found only three infected individuals among the monkeys held in captivity. The findings of this work suggest that proximity of monkeys and infected rats and their exposure to infected fleas may be responsible for the host switching of T. lewisi from their natural rodent species to primates. This and previous studies reporting T. lewisi in humans suggest that this trypanosome can cause sporadic and opportunistic flea-borne infection in primates.
Assuntos
Haplorrinos/parasitologia , Ratos Wistar/parasitologia , Trypanosoma lewisi/fisiologia , Tripanossomíase/veterinária , Animais , Brasil , DNA de Protozoário , DNA Espaçador Ribossômico , Evolução Molecular , Camundongos , Camundongos Endogâmicos BALB C , Microscopia , Filogenia , Ratos , Trypanosoma lewisi/citologia , Trypanosoma lewisi/genética , Trypanosoma lewisi/crescimento & desenvolvimento , Tripanossomíase/parasitologiaRESUMO
AIM: We estimated the number of people worldwide with diabetes for the years 2010 and 2030. METHODS: Studies from 91 countries were used to calculate age- and sex-specific diabetes prevalences, which were applied to national population estimates, to determine national diabetes prevalences for all 216 countries for 2010 and 2030. Studies were identified using Medline, and contact with all national and regional International Diabetes Federation offices. Studies were included if diabetes prevalence was assessed using a population-based methodology, and was based on World Health Organization or American Diabetes Association diagnostic criteria for at least three separate age-groups within the 20-79 year range. Self-report or registry data were used if blood glucose assessment was not available. RESULTS: The world prevalence of diabetes among adults (aged 20-79 years) will be 6.4%, affecting 285 million adults, in 2010, and will increase to 7.7%, and 439 million adults by 2030. Between 2010 and 2030, there will be a 69% increase in numbers of adults with diabetes in developing countries and a 20% increase in developed countries. CONCLUSION: These predictions, based on a larger number of studies than previous estimates, indicate a growing burden of diabetes, particularly in developing countries.
Assuntos
Diabetes Mellitus/epidemiologia , Saúde Global , Adulto , África/epidemiologia , Fatores Etários , Idoso , Europa (Continente)/epidemiologia , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Modelos Estatísticos , América do Norte/epidemiologia , Valor Preditivo dos Testes , Prevalência , Caracteres Sexuais , América do Sul/epidemiologia , Adulto JovemRESUMO
Ovarian cryobanking has considerable potential for fertility preservation and restoration and has been used to establish term pregnancies in mice, rats, sheep and humans, yet there is scope for progress towards in vitro and in vivo strategies to A) screen and improve outcomes of cryopreservation procedures and to minimize ischemic damage following grafting, B) monitor folliculogenesis and hormonal feedback, C) screen for, and remove, malignant cells, D) generate antral follicles containing normal mature fertilizable oocytes even when orthotopic autografting is not possible, and E) combine ovarian cryopreservation with more advanced reproductive technologies such as nuclear transfer (for animals only). In species such as mice a very diverse range of both cryopreservation and grafting strategies (including xenografting) has successfully generated live young. Human ovarian grafting is still a rare procedure and it is therefore encouraging that several babies have now been born. Progress has been slowest for species where compatible recipients are seldom available, such as with rare and endangered species. For these, further significant breakthroughs will be needed before cryobanked material can be reliably and efficiently used to generate new offspring.