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1.
Eur Phys J E Soft Matter ; 47(5): 29, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704810

RESUMO

In this work, we study the polarization time series obtained from experimental observation of a group of zebrafish (Danio rerio) confined in a circular tank. The complex dynamics of the individual trajectory evolution lead to the appearance of multiple characteristic scales. Employing the Multifractal Detrended Fluctuation Analysis (MF-DFA), we found distinct behaviors according to the parameters used. The polarization time series are multifractal at low fish densities and their average scales with ρ - 1 / 4 . On the other hand, they tend to be monofractal, and their average scales with ρ - 1 / 2 for high fish densities. These two regimes overlap at critical density ρ c , suggesting the existence of a phase transition separating them. We also observed that for low densities, the polarization velocity shows a non-Gaussian behavior with heavy tails associated with long-range correlation and becomes Gaussian for high densities, presenting an uncorrelated regime.


Assuntos
Fractais , Peixe-Zebra , Peixe-Zebra/fisiologia , Animais
2.
Public Health ; 233: 22-24, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38823280

RESUMO

OBJECTIVES: Fetal echocardiography is the gold standard modality to detect suspected congenital heart disease (CHD). Accurate diagnosis and subsequent prognosis is even more challenging in the presence of a raised maternal body mass index (BMI). This retrospective study aimed to gain insight into the prevalence of obesity within the cohort of patients referred for fetal echocardiography. STUDY DESIGN/METHODS: Retrospective analysis of all pregnant patients referred to the Scottish National Fetal Cardiology Service between 2015 and 2021 due to a suspected fetal cardiac abnormality and examining the associated trends in maternal BMI and the Scottish Index of Multiple Deprivation (SIMD). RESULTS: BMI data were available for 962 (96.3%) of the 998 patients referred during the study period. Median BMI during the study period was 31. BMI range in the seven-year period was 16-63. There was no association between BMI group and year (P = 0.889). A median of 58% of patients referred were classified as overweight (BMI > 25 kg/m2), and only 37% were reported to have a BMI within normal limits. Referral BMI was relatively consistent in the seven years with no dramatic increase in the obese categories. Mean BMI in SIMD 5 (lowest level of deprivation), was significantly lower (P = 0.001), than in SIMD 1 (highest deprivation). CONCLUSIONS: People of child bearing age should be aware the potential limitations that a raised BMI may have upon diagnostic/screening accuracy impacting subsequent ability to provide accurate fetal cardiac diagnoses and prognostic fetal cardiac imaging.


Assuntos
Índice de Massa Corporal , Ecocardiografia , Cardiopatias Congênitas , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Ecocardiografia/estatística & dados numéricos , Ultrassonografia Pré-Natal/estatística & dados numéricos , Escócia/epidemiologia , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/epidemiologia , Obesidade/epidemiologia , Adulto Jovem , Prevalência
3.
Public Health ; 231: 99-107, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653017

RESUMO

OBJECTIVES: During the COVID-19 pandemic, public health measures were used to reduce the spread of COVID-19; it is unknown whether people with chronic conditions differentially adhered to public health measures. The objectives of this study were to evaluate the association between chronic conditions and adherence and to explore effect modification by sex, age, and income. STUDY DESIGN: An analysis of data from the Canadian Longitudinal Study on Aging COVID-19 Questionnaires (from April to September 2020) was conducted among middle-aged and older adults aged 50-96 years (n = 28,086). METHODS: Self-reported chronic conditions included lung disease, diabetes, heart disease, cancer, obesity, anxiety, and depression. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between chronic conditions and low, medium, and high levels of adherence. Effect modification was evaluated using statistical interaction and stratification. RESULTS: Most people (n = 17,435; 62%) had at least one chronic condition, and 2866 (10%) had three to seven chronic conditions. Among those with high adherence to public health measures, 69% had one or more chronic condition (n = 2266). Having three to seven chronic conditions, compared with none, was associated with higher adherence to public health measures (OR: 2.14; 95% CI: 1.12-1.42). Higher adherence was also noted across chronic conditions, for example, those with diabetes had higher adherence (OR: 1.72; 95% CI: 1.53-1.93). There was limited evidence of effect modification by sex, age, or income. CONCLUSIONS: Canadians with chronic conditions were more likely to adhere to public health measures; however, future research is needed to understand whether adherence helped to prevent adverse COVID-19 outcomes and if adherence had unintended consequences.


Assuntos
COVID-19 , Autorrelato , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pessoa de Meia-Idade , Masculino , Canadá/epidemiologia , Feminino , Idoso , Estudos Longitudinais , Doença Crônica/epidemiologia , Idoso de 80 Anos ou mais , Saúde Pública , SARS-CoV-2
4.
Eur J Clin Microbiol Infect Dis ; 42(7): 803-818, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37093325

RESUMO

A ring trial among five European laboratories was organized to reach consistency in microsatellite (MS) typing of the zoonotic parasite Toxoplasma gondii. Three sample sets were circulated and analyzed by each laboratory following a previously published method that is based on fragment length polymorphism of 15 MS markers. The first sample set compared typing results in general and focused on effects of DNA concentration; the second sample set focused on the polymorphic fingerprinting markers that can differentiate T. gondii strains within the same archetypal lineage; and the third set focused on non-archetypal genotypes. Methodological variations between laboratories, including the software programs used to determine MS fragment length, were collated using a questionnaire. Overall, lineage-level typing results reached a high level of agreement, especially in samples with the highest DNA concentrations. However, laboratory-specific differences were observed for particular markers. Major median differences in fragment length, of up to 6 base pairs, were related to the fluorophore used to label fragment-specific primers. In addition, primer pairs with identical sequences obtained from different suppliers resulted in fragments of differing length. Furthermore, differences in the way the sequencing profiles were assessed and interpreted may have led to deviating results in fragment length determination. Harmonization of MS typing, for example, by using the same fluorophores or by numerical adjustments applied to the fragment-lengths determined, could improve the uniformity of the results across laboratories. This is the first interlaboratory comparison, providing guidelines (added as a supplement) for the optimization of this technique.


Assuntos
Toxoplasma , Toxoplasmose Animal , Humanos , Animais , Toxoplasma/genética , Variação Genética , Polimorfismo de Fragmento de Restrição , DNA de Protozoário/genética , Repetições de Microssatélites , Genótipo
5.
Can J Physiol Pharmacol ; 101(12): 620-629, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37747059

RESUMO

The purpose of this study was to characterize the role of ß1-AR signaling and its cross-talk between cardiac renin-angiotensin system and thyroid-hormone-induced cardiac hypertrophy. T3 was administered at 0.5 mg·kg-1·day-1 for 10 days in ß1-KOT3 and WTT3 groups, while control groups received vehicle alone. Echocardiography and myocardial histology was performed; cardiac and serum ANGI/ANGII and ANP and cardiac levels of p-PKA, p-ERK1/2, p-p38-MAPK, p-AKT, p-4EBP1, and ACE were measured. WTT3 showed decreased IVSTd and increased LVEDD versus WTsal (p < 0.05). ß1-KOT3 exhibited lower LVEDD and higher relative IVSTd versus ß1-KOsal, the lowest levels of ejection fraction, and the highest levels of cardiomyocyte diameter (p < 0.05). Cardiac ANP levels decreased in WTT3 versus ß1-KOT3 (p < 0.05). Cardiac ACE expression was increased in T3-treated groups (p < 0.05). Phosphorylated-p38 MAPK levels were higher in WTT3 versus WTsal or ß1-KOT3, p-4EBP1 was elevated in ß1-KO animals, and p-ERK1/2 was up-regulated in ß1-KOT3. These findings suggest that ß1-AR signaling is crucial for TiCH.


Assuntos
Cardiomiopatia Restritiva , Camundongos , Animais , Cardiomiopatia Restritiva/metabolismo , Cardiomiopatia Restritiva/patologia , Camundongos Knockout , Miocárdio/metabolismo , Hormônios Tireóideos , Receptores Adrenérgicos/metabolismo , Angiotensina II/farmacologia
6.
Phys Rev Lett ; 128(23): 236803, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35749199

RESUMO

We offer a new perspective on the problem of characterizing mesoscopic fluctuations in the interplateau regions of the integer quantum Hall transition. We found that longitudinal and transverse conductance fluctuations, generated by varying the external magnetic field within a microscopic model, are multifractal and lead to distributions of conductance increments (magnetoconductance) with heavy tails (intermittency) and signatures of a hierarchical structure (cascade) in the corresponding stochastic process, akin to Kolmogorov's theory of fluid turbulence. We confirm this picture by interpreting the stochastic process of the conductance increments in the framework of H theory, which is a continuous-time stochastic approach that incorporates the basic features of Kolmogorov's theory. The multifractal analysis of the conductance "time series," combined with the H-theory formalism, provides strong support for the overall characterization of mesoscopic fluctuations in the quantum Hall transition as a multifractal stochastic phenomenon with multiscale hierarchy, intermittency, and cascade effects.

7.
Sensors (Basel) ; 22(10)2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35632090

RESUMO

Here, we describe 4-dimethylaminoantipyrine (4-DMAA)-mediated interfacing as a broad biochemical indicator to stabilize and promote the higher response of electrodes for immunological detection. We hypothesized that the improved biological interactions of 4-DMAA with electrodes and biological samples may be due to the interaction properties of the benzene and pyrazole chemical groups with graphite and proteins, respectively. In order to demonstrate that 4-DMAA could be used as a general indicator in electrochemical immunoassays, we used peptides as probes for the diagnosis of four neglected tropical infectious diseases Tegumentary leishmaniasis, Visceral leishmaniasis, Strongyloidiasis, and Leprosy on commercial graphite screen-printed electrodes. 4-DMAA oxidation was used to indicate specific biological recognition between the epitope-based peptide and serum immunoglobulin G (IgG) from infected patients. We demonstrated that 4-DMAA should be incorporated into the electrodes prior to serum application, which avoids interference with its sensitivity and specificity. In addition, 4-DMAA oxidizes at a low anodic potential, and the oxidation peak is useful for detecting proteins in biological fluids. In summary, we have successfully demonstrated the broad application of 4-DMAA as a general indicator for the specific diagnosis of four infectious diseases in electrochemical immunosensors. Such a strategy is quite advantageous for indirect detection of proteins that lack electrochemical activities or are spatially inaccessible on the electrode surface. This new indicator opens a new avenue for monitoring biological recognition, especially for immunosensors.


Assuntos
Técnicas Biossensoriais , Grafite , Aminopirina , Eletrodos , Humanos , Imunoensaio
8.
J Med Virol ; 93(6): 3730-3737, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33368401

RESUMO

Female sex workers (FSWs) represent a high vulnerability group for the acquisition of sexual and parenteral infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. The present study aimed to determine the prevalence of serological markers and risk factors associated with exposure to HBV and HCV among FSWs in the state of Pará, Brazil. A cross-sectional study using principles of the time location sampling (TLS) method was conducted in four cities (Belém, Bragança, Barcarena, and Augusto Corrêa) of the state of Pará, from 2005 to 2006. In total, 365 FSWs were interviewed using a standardized questionnaire. Blood samples were collected and tested for serological markers of exposure to HBV and HCV using an enzyme immunoassay. The overall prevalence of exposure to HBV and HCV was 36.7% and 7.7%, respectively. The prevalence of surface antigen of HBV was 3.0%. The prevalence of anti-HBc and anti-HBc+ anti-HBs antibodies were 6.3% and 27.4%. Very few (4.7%) FSWs had vaccine immunity against HBV (anti-HBs antibodies only). The prevalence of anti-HCV antibodies was 7.7%. Low monthly income, drug usage, and unprotected sex were some of the social characteristics associated with exposure to the viruses using different analysis. The seroprevalence of HBV and HCV infections among FSWs in four cities of the state of Pará is high when compared to the general population of Brazil, but similar to those found in FSWs in other nondeveloped countries. The prevalence of HBV was higher in Belém, while the prevalence of HCV was higher in the other three cities, highlighting the importance of establishing control and prevention programs to reduce the risk of acquiring these viruses in Pará.


Assuntos
Hepatite B/epidemiologia , Hepatite B/imunologia , Hepatite C/epidemiologia , Hepatite C/imunologia , Profissionais do Sexo/estatística & dados numéricos , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Cidades/epidemiologia , Estudos Transversais , Feminino , Hepacivirus/imunologia , Hepatite B/sangue , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite C/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Estudos Soroepidemiológicos , Adulto Jovem
9.
Eur Cell Mater ; 42: 401-414, 2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825700

RESUMO

Mesenchymal stem cells (MSCs) are promising cells for regenerative medicine therapies because they can differentiate towards multiple cell lineages. However, the occurrence of cellular senescence and the acquiring of the senescence-associated secretory phenotype (SASP) limit their clinical use. Since the transcription factor TWIST1 influences expansion of MSCs, its role in regulating cellular senescence was investigated. The present study demonstrated that silencing of TWIST1 in MSCs increased the occurrence of senescence, characterised by a SASP profile different from irradiation-induced senescent MSCs. Knowing that senescence alters cellular metabolism, cellular bioenergetics was monitored by using the Seahorse XF apparatus. Both TWIST1-silencing-induced and irradiation-induced senescent MSCs had a higher oxygen consumption rate compared to control MSCs, while TWIST1-silencing-induced senescent MSCs had a low extracellular acidification rate compared to irradiation-induced senescent MSCs. Overall, data indicated how TWIST1 regulation influenced senescence in MSCs and that TWIST1 silencing-induced senescence was characterised by a specific SASP profile and metabolic state.


Assuntos
Células-Tronco Mesenquimais , Fenótipo Secretor Associado à Senescência , Senescência Celular , Metabolismo Energético , Regulação da Expressão Gênica
10.
Curr Opin Ophthalmol ; 32(3): 183-190, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33770014

RESUMO

PURPOSE OF REVIEW: Radiation therapy has become the standard of care for the treatment of uveal melanoma. We intend to outline the current radiation therapy methods that are employed to treat uveal melanoma. We will outline their relative benefits over one another. We will also provide some background about radiation therapy in general to accustom the ophthalmologists likely reading this review. RECENT FINDINGS: Four main options exist for radiation therapy of uveal melanoma. Because the eye is a small space, and because melanomas are relatively radioresistant, oncologists treating uveal melanoma must deliver highly focused doses in high amounts to a small space. Therapies incorporating external beams include proton beam therapy and stereotactic radiosurgery. Stereotactic radiosurgery comes in two forms, gamma knife therapy and cyberknife therapy. Radiation may also be placed directly on the eye surgically via plaque brachytherapy. All methods have been used effectively to treat uveal melanoma. SUMMARY: Each particular radiotherapy technique employed to treat uveal melanoma has its own set of benefits and drawbacks. The ocular oncologist can choose amongst these therapies based upon his or her clinical judgment of the relative risks and benefits. Availability of the therapy and cost to the patient remain significant factors in the ocular oncologist's choice.


Assuntos
Braquiterapia/métodos , Melanoma/radioterapia , Terapia com Prótons/métodos , Radiocirurgia/métodos , Neoplasias Uveais/radioterapia , Humanos
11.
An Acad Bras Cienc ; 93(1): e20190425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33825789

RESUMO

Conyza species are important weeds in global agriculture, especially due to their capacity to evolve resistance to multiple herbicide mechanisms of action. We aimed to evaluate the frequency and distribution of resistance to glyphosate and chlorimuron-ethyl in Conyza spp. populations from Brazil. Seed samples were collected from grain production areas across nine Brazilian states over five consecutive years (2014 to 2018). Prior to resistance monitoring trials, dose-response assays were conducted to determine a single dose of glyphosate or chlorimuron-ethyl to discriminate resistant and susceptible populations. Resistance monitoring based on plant responses to the application of discriminatory doses of glyphosate (960 g ha-1) or chlorimuron-ethyl (20 g ha-1). Populations were classified as resistant, moderately resistant, or susceptible to either herbicide. While glyphosate resistance was highly frequent (71.2%) in all the five years, chlorimuron-ethyl resistant populations occurred at 39.8% of the total. The frequency of multiple resistance to both herbicides (35.3%) was proportional to the occurrence of chlorimuron-ethyl resistance (39.6%). Resistance to glyphosate and to chlorimuron-ethyl were found across all states evaluated.


Assuntos
Conyza , Herbicidas , Brasil , Glicina/análogos & derivados , Glicina/farmacologia , Resistência a Herbicidas , Herbicidas/farmacologia , Glifosato
12.
Mol Biol Rep ; 47(11): 8645-8656, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33048324

RESUMO

This study investigated the therapeutic potential of N-acetylcysteine (NAC) in the treatment of heart failure in female rats. Myocardial infarcted (MI) rats were given NAC (250 mg/kg/day p.o.) during 28 days after surgery (MI + NAC) or vehicle (MI + Placebo), and sham-operated rats received the same treatments (Sham + NAC and Sham + Placebo). Electrocardiographic and echocardiographic analyses were performed in the last week of treatment. Cardiac mRNA levels of types I and II superoxide dismutase (SOD), catalase, types I and III glutathione peroxidase (GPX), nerve growth factor (NGF), ß1-adrenergic receptor (ß1ADR), and type 2 muscarinic receptor (M2R) were assessed. Cardiac levels NADPH oxidase (NOX) activity, total content of reduced thiols, and SOD, GPX, and catalase activity were assessed. Compared to MI + Placebo group, MI + NAC group exhibited decreased NOX activity, increased content of reduced thiols, increased GPX activity, and normalized GPX III mRNA levels (p < 0.05). Heart and lung weights, left ventricular (LV) end-diastolic volume and left atrium/aorta ratio were decreased, while LV posterior wall thickness and ejection fraction were increased in MI + NAC group versus MI + Placebo rats (p < 0.05). Power density of low frequency band was decreased, while power density of high frequency and the root mean square of the successive differences were increased in MI + NAC rats versus MI + Placebo (p < 0.05). These findings indicate that NAC promotes therapeutic effects in the progression of MI-induced heart failure in female rats.


Assuntos
Acetilcisteína , Antioxidantes , Eletrocardiografia/efeitos dos fármacos , Coração/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Feminino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
13.
Nature ; 506(7486): 76-80, 2014 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-24499918

RESUMO

Feedbacks between land carbon pools and climate provide one of the largest sources of uncertainty in our predictions of global climate. Estimates of the sensitivity of the terrestrial carbon budget to climate anomalies in the tropics and the identification of the mechanisms responsible for feedback effects remain uncertain. The Amazon basin stores a vast amount of carbon, and has experienced increasingly higher temperatures and more frequent floods and droughts over the past two decades. Here we report seasonal and annual carbon balances across the Amazon basin, based on carbon dioxide and carbon monoxide measurements for the anomalously dry and wet years 2010 and 2011, respectively. We find that the Amazon basin lost 0.48 ± 0.18 petagrams of carbon per year (Pg C yr(-1)) during the dry year but was carbon neutral (0.06 ± 0.1 Pg C yr(-1)) during the wet year. Taking into account carbon losses from fire by using carbon monoxide measurements, we derived the basin net biome exchange (that is, the carbon flux between the non-burned forest and the atmosphere) revealing that during the dry year, vegetation was carbon neutral. During the wet year, vegetation was a net carbon sink of 0.25 ± 0.14 Pg C yr(-1), which is roughly consistent with the mean long-term intact-forest biomass sink of 0.39 ± 0.10 Pg C yr(-1) previously estimated from forest censuses. Observations from Amazonian forest plots suggest the suppression of photosynthesis during drought as the primary cause for the 2010 sink neutralization. Overall, our results suggest that moisture has an important role in determining the Amazonian carbon balance. If the recent trend of increasing precipitation extremes persists, the Amazon may become an increasing carbon source as a result of both emissions from fires and the suppression of net biome exchange by drought.


Assuntos
Atmosfera/química , Ciclo do Carbono , Secas/estatística & dados numéricos , Biomassa , Biota , Brasil , Dióxido de Carbono/análise , Monóxido de Carbono/análise , Incêndios/estatística & dados numéricos , Água Doce/análise , Fotossíntese , Chuva , Estações do Ano , Árvores/metabolismo , Clima Tropical
14.
J Hum Nutr Diet ; 33(2): 274-283, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31858685

RESUMO

BACKGROUND: Malnutrition is one the greatest global health challenges of our generation, leading to the increased utilisation of healthcare resources, as well as morbidity and mortality. Research has primarily been driven by industry, academia and clinical working groups and has had little involvement from patients and carers. The project described in the present study aimed to establish a priority setting partnership allowing patients, carers and healthcare professionals an opportunity to influence the research agenda. METHODS: A national survey was conducted to gather malnutrition uncertainties and identify key issues (i.e. areas within scope where an evidence-base is lacking) from those with experience of malnutrition. Uncertainties were analysed according to themes. Similar questions were grouped and summary questions were developed. A second survey was conducted and respondents were asked to choose their 10 most important summary questions. A workshop was conducted to finalise the top 10 research priorities from the most frequently indicated uncertainties on the interim survey. RESULTS: Overall, 1128 uncertainty questions were submitted from 268 people. The interim survey had 71 responses and a list of the top 26 questions was generated for the workshop. There were 26 questions discussed, ranked and agreed by healthcare professionals, carers and patients at the workshop. The top 10 research priorities were then chosen. These included questions on oral nutritional supplements, vulnerable groups, screening, community care, use of body mass index and technology. CONCLUSIONS: The top 10 research priorities in malnutrition and nutritional screening have been identified from a robust process involving patients, carers and healthcare professionals.


Assuntos
Desnutrição , Avaliação Nutricional , Pesquisa , Participação dos Interessados , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidadores , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Pediatr Dermatol ; 36(3): 335-337, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30865309

RESUMO

Homemade "slime" is currently a popular childhood hobby that can cause allergic and irritant contact dermatitis. We describe a case of hand dermatitis due to homemade "slime" with a positive patch test to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) and MI. The most common potential allergens in "slime" collected from a review of "slime" recipes found on the Internet are reviewed.


Assuntos
Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Desinfetantes/efeitos adversos , Tiazóis/efeitos adversos , Criança , Feminino , Humanos
16.
J Virol ; 91(10)2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28275196

RESUMO

Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif (182CWAIC186) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A186, within the CX3C motif, mutating it to CX4C (182CWAIAC187), which is known to block binding to CX3CR1, might decrease disease. We studied the effect of the CX4C mutation in two strains of RSV (A2 and r19F) in a mouse challenge model. We included RSV r19F because it induces mucus production and airway resistance, two manifestations of RSV infection in humans, in mice. Compared to wild-type (wt) virus, mice infected with CX4C had a 0.7 to 1.2 log10-fold lower virus titer in the lung at 5 days postinfection (p.i.) and had markedly reduced weight loss, pulmonary inflammatory cell infiltration, mucus production, and airway resistance after challenge. This decrease in disease was not dependent on decrease in virus replication but did correspond to a decrease in pulmonary Th2 and inflammatory cytokines. Mice infected with CX4C viruses also had higher antibody titers and a Th1-biased T cell memory response at 75 days p.i. These results suggest that the CX4C mutation in the G protein could improve the safety and efficacy of a live attenuated RSV vaccine.IMPORTANCE RSV binds to the corresponding chemokine receptor, CX3CR1, through a CX3C chemokine motif (182CWAIC186) in the G protein. RSV binding to CX3CR1 contributes to disease pathogenesis; therefore, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A186, within the CX3C motif, mutating it to CX4C (182CWAIAC187), known to block binding to CX3CR1, might decrease disease. The effect of this mutation and treatment with the F(ab')2 form of the anti-RSV G 131-2G monoclonal antibody (MAb) show that mutating the CX3C motif to CX4C blocks much of the disease and immune modulation associated with the G protein and should improve the safety and efficacy of a live attenuated RSV vaccine.


Assuntos
Quimiocinas CX3C/metabolismo , Proteínas de Ligação ao GTP/genética , Mutação , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Quimiocinas CX3C/genética , Quimiocinas CX3C/imunologia , Feminino , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/imunologia , Humanos , Memória Imunológica , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Domínios e Motivos de Interação entre Proteínas , Vacinas contra Vírus Sincicial Respiratório/química , Vacinas contra Vírus Sincicial Respiratório/genética , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/fisiologia , Células Th1 , Células Th2 , Vacinas Atenuadas/química , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Replicação Viral
17.
Pediatr Diabetes ; 19(4): 656-662, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29417725

RESUMO

BACKGROUND: To assess the utility of whole-exome sequencing (WES) for mutation detection in maturity-onset diabetes of the young (MODY) and congenital hyperinsulinism (CHI). MODY and CHI are the two commonest monogenic disorders of glucose-regulated insulin secretion in childhood, with 13 causative genes known for MODY and 10 causative genes identified for CHI. The large number of potential genes makes comprehensive screening using traditional methods expensive and time-consuming. METHODS: Ten subjects with MODY and five with CHI with known mutations underwent WES using two different exome capture kits (Nimblegen SeqCap EZ Human v3.0 Exome Enrichment Kit, Nextera Rapid Capture Exome Kit). Analysis was blinded to previously identified mutations, and included assessment for large deletions. The target capture of five exome capture technologies was also analyzed using sequencing data from >2800 unrelated samples. RESULTS: Four of five MODY mutations were identified using Nimblegen (including a large deletion in HNF1B). Although targeted, one mutation (in INS) had insufficient coverage for detection. Eleven of eleven mutations (six MODY, five CHI) were identified using Nextera Rapid (including the previously missed mutation). On reconciliation, all mutations concorded with previous data and no additional variants in MODY genes were detected. There were marked differences in the performance of the capture technologies. CONCLUSIONS: WES can be useful for screening for MODY/CHI mutations, detecting both point mutations and large deletions. However, capture technologies require careful selection.


Assuntos
Hiperinsulinismo Congênito/genética , Análise Mutacional de DNA/métodos , Diabetes Mellitus Tipo 2/genética , Secreção de Insulina/genética , Sequenciamento Completo do Genoma , Adolescente , Criança , Hiperinsulinismo Congênito/metabolismo , Variações do Número de Cópias de DNA , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Mutação em Linhagem Germinativa , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Genoma/métodos
18.
Pediatr Dermatol ; 35(6): e363-e365, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30168188

RESUMO

Parry-Romberg syndrome (PRS) is characterized by progressive atrophy of facial skin, soft tissues, muscle, and bone. En coup de sabre syndrome is a form of linear scleroderma (LS) involving the skin of the frontoparietal forehead and scalp. Both conditions can be associated with neurologic findings, including seizures. We explore a case in which skin findings and seizure burden improved with methotrexate therapy.


Assuntos
Hemiatrofia Facial/complicações , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Esclerodermia Localizada/complicações , Convulsões/tratamento farmacológico , Encéfalo/patologia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Indução de Remissão , Convulsões/etiologia , Pele/patologia
19.
Parasitol Res ; 117(7): 2299-2304, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29781058

RESUMO

A Brazilian fox (Lycalopex vetulus) was rescued from a highway, and 16 days after maintained in captivity, the fox shed oocysts with sizes compatible with Hammondia sp. and Neospora caninum. DNA extracted from oocysts were initially tested in two PCRs targeting the internal transcribed spacer 1 (ITS-1) of the rDNA of Hammondia heydorni and the Nc-5 gene of N. caninum. A 270-bp product was visualized in the PCR for H. heydorni. No amplification was observed for N. caninum PCR. Since ITS-1-based PCR is not sufficient to differentiate Hammondia species derived from canids, oocyst DNA was examined using multilocus sequence analysis of five genetic fragments [intron 1 of the alpha tubulin gene (intron 1), internal transcribed spaces 1 and 2 (ITS-1 and ITS-2) of the rDNA, 28S rRNA gene (D2/D3 domain), and heat shock protein 70 (Hsp70)]. The Hammondia sp. oocyst from the Brazilian fox, referred here as H-FOXBR isolate, is closely related to H. heydorni and Hammondia triffittae, but differs from these parasites in three genetic markers (alpha tubulin gene, ITS-2, and 28S rRNA). As reported by other research groups, Hammondia spp. excreted by canids are genetically diverse and may encompass additional species besides H. heydorni and H. triffittae. In this study, we confirmed that H-FOXBR has significant genetic differences in comparison to H. heydorni and H. triffittae and may represent a separate species. Further studies are needed to identify the life cycle of this parasite and to characterize the parasite stages in the intermediate and definitive hosts.


Assuntos
Coccidiose/veterinária , Raposas/parasitologia , Oocistos/isolamento & purificação , Sarcocystidae/isolamento & purificação , Animais , Brasil , Coccidiose/parasitologia , DNA Intergênico/genética , DNA Ribossômico/genética , Fezes/parasitologia , Variação Genética , Proteínas de Choque Térmico HSP72/genética , Neospora , Reação em Cadeia da Polimerase , RNA Ribossômico 28S/genética , Sarcocystidae/genética , Tubulina (Proteína)/genética
20.
Water Environ Res ; 90(8): 685-696, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28915932

RESUMO

The hyporheic environment is composed of a rich meiofauna that depends on water flow, organic matter, and oxygen. The concentration of meiofauna varies spatially (horizontal and vertical) and temporally. Several processes occur at this interface (groundwater and surface water), including biogeochemical processes involving meiofauna. A study of the hyporheic meiofauna community in the sediments of the Beberibe River, in Brazil, was conducted. Meiofauna attained peak densities of 942.8 organisms/10 cm2, with organisms distributed over six taxa, with 98% of them represented by rotifers, nematodes, and annelids. Density was higher in the dry season with an average of 653.1 organisms/10 cm2, and in more superficial sediments with an average of 739.6 organisms/10 cm2. Greater densities were found in coarser sediment with a higher percentage of organic matter. A river bank filtration (RBF) pilot project has been installed, with good results in the attenuation of contaminants and pathogens.


Assuntos
Ecossistema , Invertebrados/fisiologia , Animais , Brasil , Projetos Piloto , Rios , Estações do Ano , Poluentes Químicos da Água/análise
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