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1.
Pestic Biochem Physiol ; 200: 105838, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582600

RESUMO

Diaspididae are one of the most serious small herbivorous insects with piercing-sucking mouth parts and are major economic pests as they attack and destroy perennial ornamentals and food crops. Chemical control is the primary management approach for armored scale infestation. However, chemical insecticides do not possess selectivity in action and not always effective enough for the control of armored scale insects. Our previous work showed that green oligonucleotide insecticides (olinscides) are highly effective against armored and soft scale insects. Moreover, olinscides possess affordability, selectivity in action, fast biodegradability, and a low carbon footprint. Insect pest populations undergo microevolution and olinscides should take into account the problem of insecticide resistance. Using sequencing results, it was found that in the mixed populations of insect pests Dynaspidiotus britannicus Newstead and Aonidia lauri Bouche, predominates the population of A. lauri. Individuals of A. lauri comprised for 80% of individuals with the sequence 3'-ATC-GTT-GGC-AT-5' in the 28S rRNA site, and 20% of the population comprised D. britannicus individuals with the sequence 3'-ATC-GTC-GGT-AT-5'. We created olinscides Diasp80-11 (5'-ATG-CCA-ACG-AT-3') and Diasp20-11 (5'-ATA-CCG-ACG-AT-3') with perfect complementarity to each of the sequences. Mortality of insects on the 14th day comprised 98.19 ± 3.12% in Diasp80-11 group, 64.66 ± 0.67% in Diasp20-11 group (p < 0.05), and 3.77 ± 0.94% in the control group. Results indicate that for maximum insecticidal effect it is necessary to use an oligonucleotide insecticide that corresponds to the dominant species. Mortality in Diasp80-11 group was accompanied with significant decrease in target 28S rRNA concentration and was 8.44 ± 0.14 and 1.72 ± 0.36 times lower in comparison with control (p < 0.05) on the 10th and 14th days, respectively. We decided to make single nucleotide substitutions in Diasp20-11 olinscide to understand which nucleotide will play the most important role in insecticidal effect. We created three sequences with single nucleotide transversion substitutions at the 5'-end - Diasp20(5')-11 (A to T), 3'-end - Diasp20(3')-11 (T to A), and in the middle of the sequence - Diasp20(6)-11 (6th nitrogenous base of the sequence; G to C), respectively. As a result, mortality of mixed population of the field experiment decreased and comprised 53.89 ± 7.25% in Diasp20(5')-11 group, 40.68 ± 4.33% in Diasp20(6)-11 group, 35.74 ± 5.51% in Diasp20(3')-11 group, and 3.77 ± 0.94% in the control group on the 14th day. Thus, complementarity of the 3'-end nucleotide to target 28S rRNA was the most important for pronounced insecticidal effect (significance of complementarity of nucleotides for insecticidal effect: 5' nt < 6 nt < 3' nt). As was found in our previous research works, the most important rule to obtain maximum insecticidal effect is complete complementarity to the target rRNA sequence and maximum coverage of target sequence in insect pest populations. However, in this article we also show that the complementarity of 3'-end is a second important factor for insecticidal potential of olinscides. Also in this article we propose 2-step DNA containment mechanism of action of olinscides, recruiting RNase H. The data obtained indicate the selectivity of olinscides and at the same time provide a simple and flexible platform for the creation of effective plant protection products, based on antisense DNA oligonucleotides.


Assuntos
Hemípteros , Inseticidas , Humanos , Animais , Inseticidas/farmacologia , Oligonucleotídeos , Nucleotídeos , RNA Ribossômico 28S , Insetos/genética , Controle de Insetos/métodos
2.
Curr Issues Mol Biol ; 45(4): 3180-3192, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37185731

RESUMO

In terms of the incidence among all tumors, skin cancer is on top, with the most deadly among them being melanoma. The search for new therapeutic agents to combat melanoma is very relevant. In our opinion, antisense oligonucleotides (ASO) aimed at suppressing the genes responsible for their viability in cancer cells give hope for treatment, which makes it possible to eliminate cancer cells near the tumor site both before and after surgery. In this article, we describe how Skeen-11 phosphorothioate oligonucleotide significantly decreased the proliferative activity of murine melanoma cells. Injections of Skeen-11 also inhibited tumor growth in mice with inoculated melanoma. A toxicity study showed no side effects with dose adjustments. The results show that the use of ASO Skeen-11 in vivo reduced the tumor size within 7 days, reduced the number of mitoses in the tumor cells, and increased the amount of necrosis compared with the control group.

3.
Int J Mol Sci ; 24(14)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37511449

RESUMO

Macrosiphoniella sanborni is a widespread pest of Chrysanthemum morifolium that causes significant damage to world floriculture. Chemical insecticides and biological methods of control have a number of disadvantages that can be improved by using oligonucleotide insecticides. In this article, we present, for the first time, the results of using oligonucleotide insecticides, for which the target sequence is an internal transcribed spacer (ITS) in a polycistronic rRNA transcript. The mortality of wingless aphid individuals after a Macsan-11 treatment was recorded at a level of 67.15 ± 3.32% 7 days after a single treatment with a solution at a concentration of 100 ng/µL and 97.38 ± 2.49% 7 days after a double treatment with a solution of the same concentration and a daily interval. The contact use of the control oligonucleotide (ACTG)2ACT-11. as well as the oligonucleotide insecticides Macsan-11(3') and Macsan-11(5') was not accompanied by insect mortality. Given the high variability in the internal transcribed spacer, which has proven to be a promising target for the action of oligonucleotide insecticides, it is possible to create selective preparations. This study showed the prospects of ribosomal insect pest genes as targets for the action of olinscides, and also demonstrated the high specificity of such insecticidal agents.


Assuntos
Afídeos , Inseticidas , Humanos , Animais , Inseticidas/farmacologia , Insetos
4.
Int J Mol Sci ; 24(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37511407

RESUMO

Climate change creates favourable conditions for the growth of insect populations. Today, the world is seeing an increase in the number of insect pest infestations associated with a long-term increase in the average temperature of climatic systems. For example, local invasions of Icerya purchasi Maskell, a citrus pest recognized worldwide, have increased in size and number in recent years. Controlling this pest is complicated because not all chemical insecticides are effective, and their use is undesirable since citrus fruit is used for food and chemical agents cumulatively harm human health. In this article, we demonstrated for the first time the successful use of a short single-stranded fragment of the 28S ribosomal RNA gene called "oligoICER-11" to control cottony cushion scale, and we propose the use of green oligonucleotide insecticides with a low carbon footprint for large-scale implementation in agriculture and forestry. Using the contact oligonucleotide insecticide oligoICER-11 at a concentration of 100 ng/µL on I. purchasi larvae resulted in a mortality of 70.55 ± 0.77% within 10 days. Thus, climate change is driving the need in both agriculture and forestry for oligonucleotide insecticides (DNA insecticides, olinscides): safe, effective, affordable insecticides with a low carbon footprint and long operational life.


Assuntos
Citrus , Hemípteros , Inseticidas , Animais , Humanos , Inseticidas/farmacologia , Oligonucleotídeos , Pegada de Carbono , Insetos
5.
Am J Epidemiol ; 191(8): 1420-1428, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35355048

RESUMO

The worldwide shortage of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while the pandemic still remains uncontrolled has led many countries to the dilemma of whether or not to vaccinate previously infected persons. Understanding the level of protection conferred by previous infection compared with that of vaccination is important for policy-making. We analyzed an updated individual-level database of the entire population of Israel to assess the protection provided by both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with coronavirus disease 2019 (COVID-19), severe disease, and death due to COVID-19. Outcome data were collected from December 20, 2020, to March 20, 2021. Vaccination was highly protective, with overall estimated effectiveness of 94.5% (95% confidence interval (CI): 94.3, 94.7) for documented infection, 95.8% (95% CI: 95.2, 96.2) for hospitalization, 96.3% (95% CI: 95.7, 96.9) for severe illness, and 96.0% (95% CI: 94.9, 96.9) for death. Similarly, the overall estimated level of protection provided by prior SARS-CoV-2 infection was 94.8% (95% CI: 94.4, 95.1) for documented infection, 94.1% (95% CI: 91.9, 95.7) for hospitalization, and 96.4% (95% CI: 92.5, 98.3) for severe illness. Our results should be considered by policy-makers when deciding whether or not to prioritize vaccination of previously infected adults.


Assuntos
COVID-19 , Vacinas Virais , Adulto , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Israel/epidemiologia , SARS-CoV-2
6.
Int J Mol Sci ; 23(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36555325

RESUMO

Insects vastly outnumber us in terms of species and total biomass, and are among the most efficient and voracious consumers of plants on the planet. As a result, to preserve crops, one of the primary tasks in agriculture has always been the need to control and reduce the number of insect pests. The current use of chemical insecticides leads to the accumulation of xenobiotics in ecosystems and a decreased number of species in those ecosystems, including insects. Sustainable development of human society is impossible without useful insects, so the control of insect pests must be effective and selective at the same time. In this article, we show for the first time a natural way to regulate the number of insect pests based on the use of extracellular double-stranded DNA secreted by the plant Pittosporum tobira. Using a principle similar to one found in nature, we show that the topical application of artificially synthesized short antisense oligonucleotide insecticides (olinscides, DNA insecticides) is an effective and selective way to control the insect Coccus hesperidum. Using contact oligonucleotide insecticide Coccus-11 at a concentration of 100 ng/µL on C. hesperidum larvae resulted in a mortality of 95.59 ± 1.63% within 12 days. Green oligonucleotide insecticides, created by nature and later discovered by humans, demonstrate a new method to control insect pests that is beneficial and safe for macromolecular insect pest management.


Assuntos
Hemípteros , Inseticidas , Animais , Humanos , Inseticidas/farmacologia , Oligonucleotídeos/farmacologia , Ecossistema , Resistência a Inseticidas , Insetos/genética , Controle de Insetos/métodos , Hemípteros/genética , Agricultura/métodos , Produtos Agrícolas/genética , DNA/farmacologia , Controle Biológico de Vetores
7.
Am J Epidemiol ; 190(3): 423-430, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997139

RESUMO

In the Tinea Capitis Study (Israel, 1966-2011), we assessed the association between childhood exposure to low to moderate doses of ionizing radiation (IR) to the head and neck and the development of vascular diseases (ischemic heart disease, carotid artery stenosis, and stroke) in adulthood. The study included 17,734 individuals from the Tinea Capitis cohort (7,408 irradiated in childhood and 10,326 nonirradiated), insured by Israel's largest health provider. Individual dosimetry was estimated based on measurements made on a head phantom and original treatment records. The mean doses were 1.5, 0.09, 0.78, and 0.017 Gy to brain, thyroid, salivary gland, and breast, respectively. Data on vascular diseases was abstracted from computerized medical records. Using Poisson regressions, we examined the association of radiation with morbidity. Any vascular disease was reported for 2,221 individuals. Adjusted for age, sex, socioeconomic status, smoking, hypertension, and diabetes, exposure to IR increased the risk of developing any vascular diseases (relative risk (RR) = 1.19, 95% confidence interval (CI): 1.09, 1.29), stroke (RR = 1.35, 1.20, 1.53), carotid artery stenosis (RR = 1.32, 1.06, 1.64), and ischemic heart disease (RR = 1.12, 1.01, 1.26). The risk of developing vascular diseases was positively associated with dose and inversely associated with age at exposure. In conclusion, the results indicate that early exposure to low to moderate doses of IR increases the risk of cerebro- and cardiovascular impairments.


Assuntos
Radiação Ionizante , Tinha do Couro Cabeludo/radioterapia , Doenças Vasculares/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lactente , Masculino , Fatores de Risco
8.
PLoS Comput Biol ; 16(3): e1007583, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32208421

RESUMO

Functional non-coding (fnc)RNAs are nucleotide sequences of varied lengths, structures, and mechanisms that ubiquitously influence gene expression and translation, genome stability and dynamics, and human health and disease. Here, to shed light on their functional determinants, we seek to exploit the evolutionary record of variation and divergence read from sequence comparisons. The approach follows the phylogenetic Evolutionary Trace (ET) paradigm, first developed and extensively validated on proteins. We assigned a relative rank of importance to every base in a study of 1070 functional RNAs, including the ribosome, and observed evolutionary patterns strikingly similar to those seen in proteins, namely, (1) the top-ranked bases clustered in secondary and tertiary structures. (2) In turn, these clusters mapped functional regions for catalysis, binding proteins and drugs, post-transcriptional modification, and deleterious mutations. (3) Moreover, the quantitative quality of these clusters correlated with the identification of functional regions. (4) As a result of this correlation, smoother structural distributions of evolutionary important nucleotides improved functional site predictions. Thus, in practice, phylogenetic analysis can broadly identify functional determinants in RNA sequences and functional sites in RNA structures, and reveal details on the basis of RNA molecular functions. As example of application, we report several previously undocumented and potentially functional ET nucleotide clusters in the ribosome. This work is broadly relevant to studies of structure-function in ribonucleic acids. Additionally, this generalization of ET shows that evolutionary constraints among sequence, structure, and function are similar in structured RNA and proteins. RNA ET is currently available as part of the ET command-line package, and will be available as a web-server.


Assuntos
Biologia Computacional/métodos , RNA/química , RNA/genética , Animais , Sítios de Ligação/genética , Evolução Biológica , Sequência Conservada , Evolução Molecular , Humanos , Modelos Moleculares , Nucleotídeos , Filogenia , Conformação Proteica , Proteínas/química , RNA não Traduzido/química , RNA não Traduzido/genética , Alinhamento de Sequência
9.
Proc Natl Acad Sci U S A ; 115(42): 10666-10671, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30266789

RESUMO

Scientific progress depends on formulating testable hypotheses informed by the literature. In many domains, however, this model is strained because the number of research papers exceeds human readability. Here, we developed computational assistance to analyze the biomedical literature by reading PubMed abstracts to suggest new hypotheses. The approach was tested experimentally on the tumor suppressor p53 by ranking its most likely kinases, based on all available abstracts. Many of the best-ranked kinases were found to bind and phosphorylate p53 (P value = 0.005), suggesting six likely p53 kinases so far. One of these, NEK2, was studied in detail. A known mitosis promoter, NEK2 was shown to phosphorylate p53 at Ser315 in vitro and in vivo and to functionally inhibit p53. These bona fide validations of text-based predictions of p53 phosphorylation, and the discovery of an inhibitory p53 kinase of pharmaceutical interest, suggest that automated reasoning using a large body of literature can generate valuable molecular hypotheses and has the potential to accelerate scientific discovery.


Assuntos
Indexação e Redação de Resumos , Quinases Relacionadas a NIMA/metabolismo , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Células HCT116 , Células HEK293 , Humanos , Quinases Relacionadas a NIMA/genética , Processamento de Linguagem Natural , Fosforilação , PubMed , Proteína Supressora de Tumor p53/genética
10.
Isr Med Assoc J ; 23(10): 611-614, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34672439

RESUMO

BACKGROUND: Israel has experienced three waves of coronavirus disease-2019 (COVID-19) infection since late February 2020, with lockdown and other measures employed to contain infection rates. In cooperation with the Israel Ministry of Health, serological testing was conducted by all four health maintenance organizations (HMO) in order to estimate national infection rates and the proportion of previously undetected disease. OBJECTIVES: To estimate the proportion of the population that was seropositive, identify factors associated with seropositive outcome, and approximate the proportion of residents that were asymptomatic. METHODS: Seroconversion rates (IgG) were measured in a representative sample of over 17,000 members of Maccabi Healthcare Services. Direct standardization was used to estimate the seropositive rates for COVID-19 infection for members of the HMO. Rates were adjusted for sensitivity and specificity of the testing products used. In addition to blood sampling, respondents were asked to complete a digital survey regarding potential exposures and symptoms experienced. RESULTS: It was estimated that 1.9% of the adult HMO population was seropositive 4 months after the first infected person was identified in the country. Seroconversion was associated with travel abroad and exposure to infected individuals. Loss of smell and taste, fever, cough, and fatigue are associated with infection. Of those found to be seropositive for COVID-19, 160 (59%) had a prior negative polymerase chain reaction (PCR) or no PCR test at all. CONCLUSIONS: Adult seropositive rates of infection were low relative to other countries. The findings suggest that early initiatives to limit infection entry and spread were effective.


Assuntos
Teste Sorológico para COVID-19 , COVID-19 , Controle de Doenças Transmissíveis , Avaliação de Sintomas , Adulto , Infecções Assintomáticas/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , Teste Sorológico para COVID-19/métodos , Teste Sorológico para COVID-19/normas , Teste Sorológico para COVID-19/estatística & dados numéricos , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/estatística & dados numéricos , Doenças Transmissíveis Importadas/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Transmissão de Doença Infecciosa/estatística & dados numéricos , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Soroconversão , Estudos Soroepidemiológicos , Avaliação de Sintomas/métodos , Avaliação de Sintomas/estatística & dados numéricos
11.
Int J Mol Sci ; 22(3)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498456

RESUMO

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund's adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Oligonucleotídeos Antissenso/uso terapêutico , Fator de Necrose Tumoral alfa/genética , Animais , Inativação Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo
12.
J Clin Microbiol ; 57(9)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31270182

RESUMO

We sought here to investigate the patterns of Staphylococcus aureus carriage in the first year of life, its determinants, and the dynamics of transmission between mothers and infants. A prospective longitudinal cohort study of S. aureus carriage among mothers and their infants was performed, including monthly screenings from pregnancy/birth through the first year of the infant's life. Medical and lifestyle data were collected. Infant S. aureus carriage was detected from rectal and nasal swabs, and maternal carriage was detected from nasal and vaginal swabs. Multivariate analysis and a nonlinear mixed model (NLMIXED) were used to determine the predictors of carriage and S. aureus persistence. Of the 671 women recruited, 130 women carried S. aureus at recruitment (19.3%); they and their 132 infants were included in the study. A total of 93% of the infants acquired S. aureus sometime during the first year of life; 64% of these infants acquired the maternal strain, mostly (66%) during the first month of life. We observed that 70 women (52.50%) and 17 infants (14%) carried S. aureus persistently. Early acquisition of S. aureus carriage was associated with longer duration of initial carriage and was the most significant predictor of S. aureus persistence, while day care center attendance was negatively associated with persistent carriage. Methicillin-resistant S. aureus was carried by two infants for only 1 month each and not by any of the mothers. Early acquisition of S. aureus, mostly from the mother, is thus an important determinant of carriage persistence in infancy.


Assuntos
Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Transmissão Vertical de Doenças Infecciosas , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Adulto , Portador Sadio/transmissão , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Mucosa Nasal/microbiologia , Estudos Prospectivos , Reto/microbiologia , Infecções Estafilocócicas/transmissão , Vagina/microbiologia , Adulto Jovem
13.
Gynecol Oncol ; 153(2): 320-325, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30872026

RESUMO

OBJECTIVE: Compare 5, 10 and 15 year survival in invasive epithelial ovarian cancer, between patients with and without BRCA1/2 germ line mutation in a nonselective group of patients diagnosed during 1994-99. METHODS: The analysis was based on 779 Jewish patients: 229 carriers to the Ashkenazi Jewish founder mutations in BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT); and 550 non-carriers. Clinical characteristics were abstracted from the patients' medical records and vital status was updated through the National Population Registry up to 11/2015. The Kaplan-Meier method, log-rank tests, and Cox-regression model were used for survival analyses. RESULTS: By the end of the follow-up period, (range 1-20 years), 629 (80.7%) deaths occurred. While considerably higher survival was observed during the first 5 years from diagnosis among carriers compared to non-carriers (46.7% vs. 36.2%, p = 0.0004), the survival rates at 15 years were 22.3% vs. 21.8% respectively (p = 0.04). The age-adjusted hazard ratio for all-cause mortality of carriers versus non-carriers was 0.74 (95%CI 0.60-0.91) in the first 5 years. For women who survived 5 and 10 years, the age-adjusted hazard ratios for mortality during 5 additional years, of carriers compared to non-carriers, were 1.38 (95%CI 0.93-2.04) and 1.08 (95%CI 0.61-1.92), respectively. CONCLUSION: The results of this study, with up to 20 years follow-up, support studies with shorter follow-up that suggested that the advantage in survival observed among BRCA1/2 carriers during the first 5 years decreases over time. Clinically, this may have implications for follow-up and therapy, especially of new agents that are particularly effective in BRCA carriers.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/mortalidade , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Testes Genéticos , Humanos , Israel/epidemiologia , Judeus/genética , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Taxa de Sobrevida , Adulto Jovem
14.
Molecules ; 24(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999681

RESUMO

Skin cancer has always been and remains the leader among all tumors in terms of occurrence. One of the main factors responsible for skin cancer, natural and artificial UV radiation, causes the mutations that transform healthy cells into cancer cells. These mutations inactivate apoptosis, an event required to avoid the malignant transformation of healthy cells. Among these deadliest of cancers, melanoma and its 'younger sister', Merkel cell carcinoma, are the most lethal. The heavy toll of skin cancers stems from their rapid progression and the fact that they metastasize easily. Added to this is the difficulty in determining reliable margins when excising tumors and the lack of effective chemotherapy. Possibly the biggest problem posed by skin cancer is reliably detecting the extent to which cancer cells have spread throughout the body. The initial tumor is visible and can be removed, whereas metastases are invisible to the naked eye and much harder to eliminate. In our opinion, antisense oligonucleotides, which can be used in the form of targeted ointments, provide real hope as a treatment that will eliminate cancer cells near the tumor focus both before and after surgery.


Assuntos
Antineoplásicos/uso terapêutico , Melanoma , Mutação , Oligonucleotídeos Antissenso/uso terapêutico , Neoplasias Cutâneas , Raios Ultravioleta/efeitos adversos , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos da radiação , Humanos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
15.
Nanomedicine ; 13(4): 1333-1339, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28115253

RESUMO

Nanoparticle-based contrast agents have been used as an imaging tool for selectively detecting cancerous processes. We aimed to evaluate the detection sensitivity of reflection measurements of gold nanorods (GNRs) bio-conjugated to anti-epidermal growth factor receptor (GNRs-EGFR) monoclonal antibodies in discriminating benign from premalignant and malignant human oral lesions. Tissue sections incubated with GNRs-EGFR and the reflectance spectrum was measured using hyperspectral microscopy. Reflectance intensity increased with the progression of the disease, lowest in the control group and increasing as the dysplastic changes increase (P<0.001 for linear trend of grade). Intensity was significantly higher in the moderate and severe dysplasias and cancer patients than in the controls and mild dysplasia (t test P=0.0003, Mann-Whitney P<0.0001). The GNRs reflection measurements can discriminate benign and mild dysplastic lesions from the more severe dysplasia and invasive cancer, suggesting an objective, not dependent on the qualification of a technician and with less interpretation errors.


Assuntos
Anticorpos Monoclonais/química , Carcinoma de Células Escamosas/diagnóstico , Ouro/química , Neoplasias Bucais/diagnóstico , Nanotubos/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Genes Chromosomes Cancer ; 55(9): 710-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27152944

RESUMO

The most common translocation in multiple myeloma (MM) is t(11;14)(q13;q32). According to several studies, this translocation represents a unique subset of patients with relatively favorable outcomes. Using combined analyses of morphology and fluorescence in situ hybridization (I-FISH), we examined the co-occurrence rates of t(11;14) with seven chromosomal aberrations (CAs), del(13q), del(17p), del(1p), gain(1q), multiple gains(1q), del(16q), and del(IGH), and assessed the effect of the different combinations on patient outcomes, with overall survival (OS) as the main outcome measure. Bone marrow samples and clinical data from 212 patients with MM with t(11;14) were analyzed. At least two additional CAs were found in 35% (75/205) of patients and a strong correlation between specific CAs. The occurrence of three CAs [multiple gains of (1q) (HR = 6.94, P = 0.001), del(1p) (HR = 4.47, P = 0.008), and del(IGH) (HR = 2.38, P = 0.002)] exerted a profoundly deleterious effect on median OS when compared with patients with t(11;14) only. Del(17p) and del(13q) have also exerted a deleterious effect albeit to a lesser extent (HR = 2.05, P = 0.07 and HR = 1.81, P = 0.03, respectively). When compared with t(11;14) alone, the addition of certain CAs lead to worse outcomes. These findings may have important clinical and biological implications. Patients with coexisting adverse lesions and t(11;14) may be considered at high risk and managed accordingly. © 2016 Wiley Periodicals, Inc.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 14/genética , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Translocação Genética/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
Stat Med ; 34(25): 3349-61, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26033190

RESUMO

In this work, we describe a two-stage sampling design to estimate the infection prevalence in a population. In the first stage, an imperfect diagnostic test was performed on a random sample of the population. In the second stage, a different imperfect test was performed in a stratified random sample of the first sample. To estimate infection prevalence, we assumed conditional independence between the diagnostic tests and develop method of moments estimators based on expectations of the proportions of people with positive and negative results on both tests that are functions of the tests' sensitivity, specificity, and the infection prevalence. A closed-form solution of the estimating equations was obtained assuming a specificity of 100% for both tests. We applied our method to estimate the infection prevalence of visceral leishmaniasis according to two quantitative polymerase chain reaction tests performed on blood samples taken from 4756 patients in northern Ethiopia. The sensitivities of the tests were also estimated, as well as the standard errors of all estimates, using a parametric bootstrap. We also examined the impact of departures from our assumptions of 100% specificity and conditional independence on the estimated prevalence.


Assuntos
Viés , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/epidemiologia , Métodos Epidemiológicos , Estudos de Coortes , Testes Diagnósticos de Rotina , Etiópia/epidemiologia , Humanos , Leishmaniose Visceral/sangue , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Modelos Estatísticos , Reação em Cadeia da Polimerase , Prevalência , Probabilidade , Tamanho da Amostra , Sensibilidade e Especificidade
18.
J Ultrasound Med ; 33(8): 1441-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25063409

RESUMO

OBJECTIVES: Elastography assesses the strain of soft tissues and is used to enhance diagnostic accuracy in evaluating breast tumors, but minimal data exist on its ability to accurately assess tumor size. This study was performed to assess the preoperative accuracy of measuring the size of biopsyproven breast cancer lesions with elastography and conventional B-mode sonography compared with the reference standard size measured by histopathologic examination. METHODS: Elastography and conventional B-mode sonography were performed on 69 women with histologically proven breast cancer, and tumor sizes on both modalities were recorded. These measurements were compared with the final pathologic size, which was used as the reference standard. The sizes and differences between sonographic, elastographic, and pathologic measurements were statistically tested, and an analysis of equivalence to the reference standard was performed using Bland-Altman plots. RESULTS: There was a significant difference between sizes on elastography and pathologic examination, with elastography overestimating the tumor size (P = .0187). Sonography slightly underestimated the tumor size, but this finding was not significant (P = .36). Bland-Altman plots confirmed that sonography but not elastography was an acceptable standard compared with the pathologic size. CONCLUSIONS: Breast elastography but not B-mode sonography overestimates the size of breast tumors compared with the final pathologic size.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Carga Tumoral/fisiologia , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/ultraestrutura , Diagnóstico Diferencial , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Adv Mater ; 36(24): e2313830, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38588005

RESUMO

This study pioneers a chemical sensor based on surfactant-free aerosol-synthesized single-walled carbon nanotube (SWCNT) films for detecting nitrogen dioxide (NO2). Unlike conventional CNTs, the SWCNTs used in this study exhibit one of the highest surface-to-volume ratios. They show minimal bundling without the need for surfactants and have the lowest number of defects among reported CNTs. Furthermore, the dry-transferrable and facile one-step lamination results in promising industrial viability. When applied to devices, the sensor shows excellent sensitivity (41.6% at 500 ppb), rapid response/recovery time (14.2/120.8 s), a remarkably low limit of detection (below ≈0.161 ppb), minimal noise, repeatability for more than 50 cycles without fluctuation, and long-term stability for longer than 6 months. This is the best performance reported for a pure CNT-based sensor. In addition, the aerosol SWCNTs demonstrate consistent gas-sensing performance even after 5000 bending cycles, indicating their suitability for wearable applications. Based on experimental and theoretical analyses, the proposed aerosol CNTs are expected to overcome the limitations associated with conventional CNT-based sensors, thereby offering a promising avenue for various sensor applications.

20.
Nutr J ; 12: 12, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23317009

RESUMO

OBJECTIVE: Body mass index (BMI) is more commonly used than waist circumference as a measure of adiposity in clinical and research settings. The purpose of this study was to compare the associations of BMI and waist circumference with cardiorespiratory fitness. METHODS: In a cross-sectional study of 403 healthy men and women aged 50 ± 8.8 years, BMI and waist circumference were measured. Cardiorespiratory fitness was assessed from estimated maximal O2 uptake (VO2max), as calculated from a maximal fitness test. RESULTS: Mean BMI (kg/m2) was 27.8 ± 3.7 and 25.5 ± 4.6; and mean waist circumference (cm) 94.1 ± 9.7 and 84.3 ± 10.4 for men and women, respectively. Both men and women reported an average of 2.5 hours of weekly sports related physical activity, and 18% were current smokers. Correlation coefficients between both BMI and waist circumference, and VO2max were statistically significant in men (r= -0.280 and r= -0.377, respectively, p>0.05 for both) and in women (r= -0.514 and r= -0.491, respectively, p>0.05 for both). In women, the contribution of BMI to the level of VO2max in a regression model was greater, while in men waist circumference contributed more to the final model. In these models, age, hours of training per week, and weekly caloric expenditure in sport activity, significantly associated with VO2max, while smoking did not. CONCLUSION: The differences observed between the sexes in the associations of BMI and waist circumference with VO2max support the clinical use of both obesity measures for assessment of cardiorespiratory fitness.


Assuntos
Índice de Massa Corporal , Nível de Saúde , Aptidão Física , Circunferência da Cintura , Adulto , Idoso , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/prevenção & controle , Consumo de Oxigênio
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