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Evolutionarily conserved structural folds can give rise to diverse biological functions, yet predicting atomic-scale interactions that contribute to the emergence of novel activities within such folds remains challenging. Pancreatic-type ribonucleases illustrate this complexity, sharing a core structure that has evolved to accommodate varied functions. In this study, we used ancestral sequence reconstruction to probe evolutionary and molecular determinants that distinguish biological activities within eosinophil members of the RNase 2/3 subfamily. Our investigation unveils functional, structural, and dynamical behaviors that differentiate the evolved ancestral ribonuclease (AncRNase) from its contemporary eosinophil RNase orthologs. Leveraging the potential of ancestral reconstruction for protein engineering, we used AncRNase predictions to design a minimal 4-residue variant that transforms human RNase 2 into a chimeric enzyme endowed with the antimicrobial and cytotoxic activities of RNase 3 members. This work provides unique insights into mutational and evolutionary pathways governing structure, function, and conformational states within the eosinophil RNase subfamily, offering potential for targeted modulation of RNase-associated functions.
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Eosinófilos , Humanos , Sequência de Aminoácidos , Eosinófilos/metabolismo , Eosinófilos/enzimologia , Evolução Molecular , Ribonucleases/metabolismo , Ribonucleases/química , Ribonucleases/genética , Animais , Macaca fascicularis , Filogenia , Modelos Moleculares , Estrutura Terciária de ProteínaRESUMO
Bacteriophage L522, which infects Xanthomonas oryzae pv. oryzae, was isolated from a paddy leaf sample collected in Long An province, Vietnam. The phage shows myovirus morphology based on transmission electron microscopy. It displays a latent period and burst size of approximately 3 h and 63 new virions per infected cell (PFU/infected cell), respectively. The genome of L522 is 44,497 bp in length, with 52% GC content. Of the 63 genes identified, functions were predicted for 26. No virulence or antibiotic-resistance genes were detected. The results of a BLASTn search showed similarity to a previously reported Xanthomonas phage, with 85% average nucleotide sequence identity and 87.15% query coverage. Thus, this L522 is a representative of a new species in the genus Xipdecavirus.
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Bacteriófagos , Oryza , Siphoviridae , Xanthomonas , Bacteriófagos/genética , Xanthomonas/genéticaRESUMO
The design of allosteric modulators to control protein function is a key objective in drug discovery programs. Altering functionally essential allosteric residue networks provides unique protein family subtype specificity, minimizes unwanted off-target effects, and helps avert resistance acquisition typically plaguing drugs that target orthosteric sites. In this work, we used protein engineering and dimer interface mutations to positively and negatively modulate the immunosuppressive activity of the proapoptotic human galectin-7 (GAL-7). Using the PoPMuSiC and BeAtMuSiC algorithms, mutational sites and residue identity were computationally probed and predicted to either alter or stabilize the GAL-7 dimer interface. By designing a covalent disulfide bridge between protomers to control homodimer strength and stability, we demonstrate the importance of dimer interface perturbations on the allosteric network bridging the two opposite glycan-binding sites on GAL-7, resulting in control of induced apoptosis in Jurkat T cells. Molecular investigation of G16X GAL-7 variants using X-ray crystallography, biophysical, and computational characterization illuminates residues involved in dimer stability and allosteric communication, along with discrete long-range dynamic behaviors involving loops 1, 3, and 5. We show that perturbing the protein-protein interface between GAL-7 protomers can modulate its biological function, even when the overall structure and ligand-binding affinity remains unaltered. This study highlights new avenues for the design of galectin-specific modulators influencing both glycan-dependent and glycan-independent interactions.
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Apoptose , Galectinas , Tolerância Imunológica , Multimerização Proteica , Linfócitos T/imunologia , Regulação Alostérica , Apoptose/genética , Apoptose/imunologia , Galectinas/química , Galectinas/genética , Galectinas/imunologia , Humanos , Células Jurkat , Multimerização Proteica/genética , Multimerização Proteica/imunologiaRESUMO
BACKGROUND: In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes. METHODS: In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death. RESULTS: Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).
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Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Compostos Benzidrílicos/efeitos adversos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/mortalidade , Terapia Combinada , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Feminino , Glucosídeos/efeitos adversos , Hemoglobinas Glicadas/análise , Insuficiência Cardíaca/complicações , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/tratamento farmacológicoRESUMO
A 41-year-old man from Son La Province, Vietnam, sought care for disseminated prurigo-like skin lesions from which nematode larvae were emerging. We morphologically and molecularly identified the larvae as Oxyspirura sp. Our findings confirm this nematode species as a zoonotic pathogen for emerging disease.
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Doenças das Aves , Thelazioidea , Adulto , Animais , Humanos , Larva , Masculino , Prurido , Vietnã/epidemiologiaRESUMO
OBJECTIVES: To document the prevalence of overweight and obesity and examine associated risk factors. STUDY DESIGN: A cross-sectional survey was conducted in 16 primary public schools in eight districts of Ho Chi Minh City in 2016. A multistage clustering sampling method was used to collect a sample of 1806 pupils attending the first, second, and third grades (7-9 years). METHODS: Age- and sex-adjusted body mass index (BMI) status was defined using International Obesity Taskforce cut-offs. Ordered probit regression models were used to assess the association between child BMI and its socio-economic and demographic risk factors. The model was estimated separately for boys and girls to assess the extent to which the socio-economic gradients in BMI vary by gender. RESULTS: The prevalence of obesity among boys was twice the rate for girls (24.7 vs 12.3%). The prevalence of overweight and obesity were also higher among pupils attending schools located in urban districts than in semi-rural districts. Gender, household wealth, the frequency of having breakfast at home, parental body weight, and school location were strong predictors of child BMI status. The protective effect of having breakfast more frequently at home against the risk of overweight/obesity was more pronounced in girls than in boys. Father's body weight and child BMI were more strongly associated with boys from poorer households than boys from wealthier households, while the differences were not significant for girls. CONCLUSIONS: The high prevalence of childhood overweight and obesity indicates an urgent need for more gender-specific, effective intervention, and prevention programs.
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Índice de Massa Corporal , Obesidade/epidemiologia , Obesidade Infantil/epidemiologia , Adolescente , Peso Corporal , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , População Rural , Instituições Acadêmicas , Inquéritos e Questionários , Vietnã/epidemiologiaRESUMO
Interactions of dimethyl sulfoxide with carbon dioxide and water molecules which induce 18 significantly stable complexes are thoroughly investigated. An addition of CO2 or H2 O molecules into the DMSOâ¯1CO2 and DMSOâ¯1H2 O systems leads to an increase in the stability of the resulting complexes, in which it is larger for a H2 O addition than a CO2 . The overall stabilization energy of the DMSOâ¯1,2CO2 is mainly contributed by the S=Oâ¯C Lewis acid-base interaction, whereas the O - Hâ¯O hydrogen bond plays a significant role in stabilizing complexes of DMSOâ¯1,2H2 O and DMSOâ¯1CO2 â¯1H2 O. Remarkably, the complexes of DMSOâ¯2H2 O are found to be more stable than DMSOâ¯1CO2 â¯1H2 O and DMSOâ¯2CO2 . The level of the cooperativity of multiple interactions in ternary complexes tends to decrease in going from DMSOâ¯2H2 O to DMSOâ¯1CO2 â¯1H2 O and finally to DMSOâ¯2CO2 . It is generally found that the red shift of the O - H bond involved in an O - Hâ¯O hydrogen bond increases while the blue shift of a C - H bond in a C - Hâ¯O hydrogen bond decreases when a cooperative effect occurs in ternary complexes as compared to those of the corresponding binary complexes. © 2018 Wiley Periodicals, Inc.
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BACKGROUND: As part of a targeted malaria elimination project, mass drug administrations (MDAs) were conducted in Vietnam. The impact of MDAs on malaria transmission depends largely on the efficacy of the anti-malarial drug regimen, the malaria epidemiology in the site and the population coverage. To explore why some people participate in MDAs and others do not, a quantitative survey of the villagers' perceptions was undertaken in Vietnam. METHODS: In 2013/2014 MDAs were conducted in a village in Binh Phuoc province and a village in Ninh Thuan province. Within three months of the drug administration, 59 respondents in a village in Binh Phuoc and 79 respondents in a village in Ninh Thuan were randomly selected and interviewed. RESULTS: Comprehension of the purpose of the intervention was of paramount importance for participation in the intervention. Respondents aware that the intervention aims to protect against malaria were significantly more likely to participate than respondents who were unaware of the MDA's purpose. Secondly, how and by whom villagers were informed was critical for participation. There was a strong association between sensitization by an informant such as a member of the local health team with participation in the intervention. CONCLUSIONS: The study suggests several approaches to increase participation in mass drug administration campaigns. Training trustworthy informants to sensitize the study population is critical to maximize village participation in this setting. To achieve high coverage the entire community must understand and agree with the intervention.
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Antimaláricos/administração & dosagem , Quimioprevenção/métodos , Transmissão de Doença Infecciosa/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Malária/tratamento farmacológico , Malária/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , População Rural , VietnãRESUMO
BACKGROUND AND AIM OF THE STUDY: Progression of tricuspid regurgitation (TR) may occur after mitral valve replacement (MVR). The study aim was to define the independent predictors for new severe TR after MVR to treat rheumatic heart disease. METHODS: A total of 413 patients (177 men, 236 women; mean age 40.9 ± 9.2 years) with rheumatic heart disease undergoing MVR without concomitant tricuspid valve repair at the authors' institute between 1995 and 2005, who did not have preoperative severe TR, were followed for at least one year postoperatively. Survival without severe TR was estimated using the Kaplan-Meier method. Independent predictors for new severe TR were identified using multiple Cox regression analysis. RESULTS: During a median follow up of 13 years there were two late deaths, and 46 patients (11.1%) had new severe TR. Survival without severe TR was 88.0 ± 1.7% at 10 years. Independent predictors for new severe TR were preoperative moderate TR (HR 2.401; p = 0.008) and atrial fibrillation (AF) (HR 2.119; p = 0.018). At the most recent follow up, furosemide was used in 23.9% patients with and 7.3% patients without new severe TR (p = 0.001). Patients with new severe TR had larger right ventricles and higher pulmonary artery pressures on echocardiography. CONCLUSIONS: Among patients with rheumatic heart disease undergoing MVR without concomitant tricuspid valve repair, independent predictors for new severe TR were preoperative moderate TR and AF. New severe TR was associated with increased furosemide use.
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Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Cardiopatia Reumática/cirurgia , Insuficiência da Valva Tricúspide/fisiopatologia , Valva Tricúspide/fisiopatologia , Adulto , Distribuição de Qui-Quadrado , Progressão da Doença , Ecocardiografia Doppler , Feminino , Furosemida/uso terapêutico , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/mortalidade , Insuficiência da Valva Mitral/fisiopatologia , Modelos de Riscos Proporcionais , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/mortalidade , Cardiopatia Reumática/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/mortalidadeRESUMO
Molecular epidemiology and clinical impact of human rhinovirus (HRV) are not well documented in tropical regions. This study compared the clinical characteristics of HRV to other common viral infections and investigated the molecular epidemiology of HRV in hospitalized children with acute respiratory infections (ARIs) in Vietnam. From April 2010 to May 2011, 1082 nasopharyngeal swabs were screened for respiratory viruses by PCR. VP4/VP2 sequences of HRV were further characterized. HRV was the most commonly detected virus (30%), in which 70% were diagnosed as either pneumonia or bronchiolitis. Children with single HRV infections presented with significantly higher rate of hypoxia than those infected with respiratory syncytial virus or parainfluenza virus (PIV)-3 (12·4% vs. 3·8% and 0%, respectively, P < 0·05), higher rate of chest retraction than PIV-1 (57·3% vs. 34·5%, P = 0·028), higher rate of wheezing than influenza A (63·2% vs. 42·3%, P = 0·038). HRV-C did not differ to HRV-A clinically. The genetic diversity and changes of types over time were observed and may explain the year-round circulation of HRV. One novel HRV-A type was discovered which circulated locally for several years. In conclusion, HRV showed high genetic diversity and was associated with significant morbidity and severe ARIs in hospitalized children.
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Infecções por Picornaviridae/epidemiologia , Rhinovirus/genética , Proteínas Virais/genética , Doença Aguda/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Variação Genética , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Dados de Sequência Molecular , Filogenia , Síndrome do Desconforto Respiratório , Rhinovirus/metabolismo , Análise de Sequência de RNA , Vietnã/epidemiologiaRESUMO
Information about viral acute respiratory infections (ARIs) is essential for prevention, diagnosis and treatment, but it is limited in tropical developing countries. This study described the clinical and epidemiological characteristics of ARIs in children hospitalized in Vietnam. Nasopharyngeal samples were collected from children with ARIs at Ho Chi Minh City Children's Hospital 2 between April 2010 and May 2011 in order to detect respiratory viruses by polymerase chain reaction. Viruses were found in 64% of 1082 patients, with 12% being co-infections. The leading detected viruses were human rhinovirus (HRV; 30%), respiratory syncytial virus (RSV; 23·8%), and human bocavirus (HBoV; 7·2%). HRV was detected all year round, while RSV epidemics occurred mainly in the rainy season. Influenza A (FluA) was found in both seasons. The other viruses were predominant in the dry season. HRV was identified in children of all age groups. RSV, parainfluenza virus (PIV) 1, PIV3 and HBoV, and FluA were detected predominantly in children aged 24 months, respectively. Significant associations were found between PIV1 with croup (P < 0·005) and RSV with bronchiolitis (P < 0·005). HBoV and HRV were associated with hypoxia (P < 0·05) and RSV with retraction (P < 0·05). HRV, RSV, and HBoV were detected most frequently and they may increase the severity of ARIs in children.
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DNA Viral/análise , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Doença Aguda , Adolescente , Bronquiolite/virologia , Criança , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/virologia , Tosse/virologia , Crupe/virologia , Feminino , Hospitalização , Bocavirus Humano/isolamento & purificação , Humanos , Hipóxia/virologia , Lactente , Vírus da Influenza A/isolamento & purificação , Influenza Humana/complicações , Influenza Humana/epidemiologia , Masculino , Nasofaringe/virologia , Vírus da Parainfluenza 1 Humana/isolamento & purificação , Vírus da Parainfluenza 3 Humana/isolamento & purificação , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/epidemiologia , Infecções por Picornaviridae/complicações , Infecções por Picornaviridae/epidemiologia , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções por Respirovirus/complicações , Infecções por Respirovirus/epidemiologia , Rhinovirus/isolamento & purificação , Estações do Ano , Vietnã/epidemiologiaRESUMO
OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.
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Anticorpos Antinucleares/sangue , Complemento C1q/imunologia , DNA/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Estudos de Casos e Controles , Proteínas do Sistema Complemento/deficiência , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/etnologia , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Proteinúria/sangue , Doenças Reumáticas/imunologia , Sensibilidade e Especificidade , Adulto JovemRESUMO
INTRODUCTION: The U.S. Environmental Protection Agency's (EPA's) Toxicity Forecaster (ToxCast) is a potential tool for chemical prioritization, hazard identification, and risk assessment. We conducted a case study to compare ToxCast data with endpoints from other in vitro and in vivo studies for two data-rich pesticides: endosulfan and methidathion. METHODS: ToxCast assays for endocrine disruption, development (zebrafish), and neurotoxicity were qualitatively compared to traditional neurotoxicity, developmental and reproductive toxicity findings. We also used in vitro-in vivo extrapolation to convert half-maximal activity concentrations in active ToxCast assays to rat oral equivalent doses, and quantitatively compared these to the lowest observable effect level (LOEL) from in vivo studies. RESULTS: Endosulfan was inactive for GABAA R, unlike in vivo; but active with dopamine transporter assays and was neurotoxic in zebrafish as expected. Methidathion was not active for these endpoints in vivo or in vitro. Acetylcholinesterase inhibition was ToxCast-inactive, although both pesticides are inhibitors in vivo. ToxCast results were generally inactive for endosulfan estrogen receptor agonism and androgen receptor antagonism unlike in vivo. Calculated oral equivalent doses for estrogen receptor and androgen receptor pathways and for zebrafish assays for both compounds were generally consistent with in vivo LOELs. Endosulfan showed neurotoxicity and both pesticides showed developmental effects in the zebrafish assays, although methidathion is not developmentally toxic in vivo. CONCLUSIONS: ToxCast's predictions showed concordance on some endpoints and nonconcordance, consisting mainly of false inactives, in several critical endpoints, likely due to a lack of metabolic activation and limitations in assay design. Zebrafish assays were good predictors of developmental toxicity and neurotoxicity for endosulfan.
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Desenvolvimento Embrionário/efeitos dos fármacos , Sistema Endócrino/efeitos dos fármacos , Endossulfano/toxicidade , Sistema Nervoso/efeitos dos fármacos , Compostos Organotiofosforados/toxicidade , Testes de Toxicidade/métodos , Peixe-Zebra/crescimento & desenvolvimento , Animais , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Humanos , Técnicas In Vitro , Inseticidas/toxicidade , Camundongos , Coelhos , Ratos , Medição de RiscoAssuntos
Saúde Pública , Instituições Acadêmicas , Índice de Massa Corporal , Criança , Humanos , VietnãRESUMO
In the experiments of neutron interaction with research samples, the incident neutron energy spectrum, distribution inside the irradiating sample volume, is affected by the unexpected neutron self-shielding effects. The nature of these effects is due to the formation and thickness of the irradiating sample, which significantly causes neutron self-absorption and multiple scattering inside the sample volume. The datasets presented in this article showed the thermal (Gth) and epithermal (Gepi) neutron self-shielding correction factors for the 186W(n,γ)187W neutron capture reaction rate in irradiating tungsten (W) foil samples with different thicknesses. The simulations were performed for three models of surface neutron source's geometries and relative orientations of the irradiating foil samples of isotropic cylinder surface neutron source with foil sample along to the center line, isotropic cylinder neutron source with foil sample flat to the center line, and isotropic spherical neutron source with foil sample placed at the center point. The range of sample thicknesses was from 10 µm to 2.5 mm. The uncertainties for each data point are also reported in the data table, making it more convenient for reuse in related experiments or evaluations.
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BACKGROUND: In northern Vietnam the Neonatal health - Knowledge Into Practice (NeoKIP, Current Controlled Trials ISRCTN44599712) trial has evaluated facilitation as a knowledge translation intervention to improve neonatal survival. The results demonstrated that intervention sites, each having an assigned group including local stakeholders supported by a facilitator, lowered the neonatal mortality rate by 50% during the last intervention year compared with control sites. This process evaluation was conducted to identify and describe mechanisms of the NeoKIP intervention based on experiences of facilitators and intervention group members. METHODS: Four focus group discussions (FGDs) were conducted with all facilitators at different occasions and 12 FGDs with 6 intervention groups at 2 occasions. Fifteen FGDs were audio recorded, transcribed verbatim, translated into English, and analysed using thematic analysis. RESULTS: Four themes and 17 sub-themes emerged from the 3 FGDs with facilitators, and 5 themes and 18 sub-themes were identified from the 12 FGDs with the intervention groups mirroring the process of, and the barriers to, the intervention. Facilitators and intervention group members concurred that having groups representing various organisations was beneficial. Facilitators were considered important in assembling the groups. The facilitators functioned best if coming from the same geographical area as the groups and if they were able to come to terms with the chair of the groups. However, the facilitators' lack of health knowledge was regarded as a deficit for assisting the groups' assignments. FGD participants experienced the NeoKIP intervention to have impact on the knowledge and behaviour of both intervention group members and the general public, however, they found that the intervention was a slow and time-consuming process. Perceived facilitation barriers were lack of money, inadequate support, and the function of the intervention groups. CONCLUSIONS: This qualitative process evaluation contributes to explain the improved neonatal survival and why this occurred after a latent period in the NeoKIP project. The used knowledge translation intervention, where facilitators supported multi-stakeholder coalitions with the mandate to impact upon attitudes and behaviour in the communes, has low costs and potential for being scaled-up within existing healthcare systems.
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Centros Comunitários de Saúde , Países em Desenvolvimento , Mortalidade Infantil , Avaliação de Programas e Projetos de Saúde , Comunicação , Comportamento Cooperativo , Grupos Focais , Implementação de Plano de Saúde/economia , Acessibilidade aos Serviços de Saúde , Humanos , Recém-Nascido , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Resolução de Problemas , Pesquisa Qualitativa , Pesquisa Translacional Biomédica , VietnãRESUMO
The genus Elsinoe includes many aggressive plant pathogens that infect various economically important agricultural, horticultural and forestry plants. Significant diseases include citrus scab caused by E. fawcettii and E. australis, grapevine spot anthracnose by E. ampelina, and the emerging Eucalyptus scab and shoot malformation disease caused by the recently described E. necatrix. Despite their importance as plant pathogens, little is known regarding the biology of many Elsinoe spp. To gain insights into the reproductive biology of these fungi, we characterized the mating-type loci of seven species using whole genome sequence data. Results showed that the MAT1 locus organization and its flanking genes is relatively conserved in most cases. All seven species manifested a typical heterothallic mating system characterized by having either the MAT1-1 or MAT1-2 idiomorph present in an isolate. These idiomorphs were defined by the MAT1-1-1 or the MAT1-2-1 gene, respectively. A unique MAT1-1 idiomorph containing a truncated MAT1-2-1 gene, and a MAT1-1-1 gene, was identified in E. necatrix and E. fawcettii genomes. Additionally, two idiomorph-specific proteins were found in the MAT1-1 and MAT1-2 idiomorphs of E. australis. Universal mating-type markers confirmed heterothallism across 21 Elsinoe spp., are poised to advance future studies regarding the biology of these fungi.
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Ascomicetos , Genes Fúngicos Tipo Acasalamento , Ascomicetos/genética , Reprodução/genéticaRESUMO
Euphorbia mauritanica is a succulent shrub that is indigenous to South Africa and widely distributed throughout the country. Dying plants have been observed in their natural habitat in the Northern and Western Cape Provinces of South Africa in recent years. Stems displaying lesions were collected and the emerging cultures were identified based on ITS, LSU, ACT, RPB2, TEF1 and/or TUB2 sequence data. Four filamentous fungi were consistently observed and isolated. One was identified as Alanphillipsia (Ala.) aloes, and the other three were new to science and are described here as Cytospora euphorbiicola sp. nov., Nothomicrosphaeropsis namakwaensis sp. nov. and Austrophoma (Aus.) euphorbiae gen. et sp. nov. These new species and Ala. aloes were the most commonly encountered, and their pathogenicity was tested on E. mauritanica plants in a greenhouse trial. All four species gave rise to lesions that were significantly larger than those associated with the controls, but they were not significantly different to each other. Although the lesions associated with the inoculations were well-developed, they did not give rise to plant death, suggesting that they are not responsible for the large-scale die-off of E. mauritanica in the field. The primary cause of the death of E. mauritanica in the studied area remains unknown and could be due to environmental factors such as has been found with the die-off of Euphorbia ingens in South Africa. Citation: Marincowitz S, Pham NQ, Wingfield BD, Roets F, Wingfield MJ (2023). Microfungi associated with dying Euphorbia mauritanica in South Africa and their relative pathogenicity. Fungal Systematics and Evolution 12: 59-71. doi: 10.3114/fuse.2023.12.04.
RESUMO
Clinical adoption of an artificial intelligence-enabled imaging tool requires critical appraisal of its life cycle from development to implementation by using a systematic, standardized, and objective approach that can verify both its technical and clinical efficacy. Toward this concerted effort, the ASFNR/ASNR Artificial Intelligence Workshop Technology Working Group is proposing a hierarchal evaluation system based on the quality, type, and amount of scientific evidence that the artificial intelligence-enabled tool can demonstrate for each component of its life cycle. The current proposal is modeled after the levels of evidence in medicine, with the uppermost level of the hierarchy showing the strongest evidence for potential impact on patient care and health care outcomes. The intended goal of establishing an evidence-based evaluation system is to encourage transparency, foster an understanding of the creation of artificial intelligence tools and the artificial intelligence decision-making process, and to report the relevant data on the efficacy of artificial intelligence tools that are developed. The proposed system is an essential step in working toward a more formalized, clinically validated, and regulated framework for the safe and effective deployment of artificial intelligence imaging applications that will be used in clinical practice.
Assuntos
Inteligência Artificial , Diagnóstico por Imagem , HumanosRESUMO
Cankers leading to branch, stem and plant death were observed on the South African endemic Rafnia amplexicaulis (Fabaceae) in the Cederberg Wilderness Area, South Africa, during September 2021. Conidiomatal pycnidia were found developing on the cankers, and isolations consistently yielded a Microsphaeropsis species. Phylogenetic analysis based on partial nucleotide sequences of the internal transcribed spacers (ITS), the nuclear large subunit (LSU) and RNA polymerase II second largest subunit (RPB2) regions showed that the fungus represented an undescribed species. Based on the multigene phylogeny and morphological characteristics, we describe the species here as M. rafniae sp. nov. Pathogenicity tests and the fulfilment of Koch's postulates confirmed that M. rafniae sp. nov. is the cause of the cankers of R. amplexicaulis. Presently, this disease is known from a single location in South Africa, and further surveys are required to determine its distribution and relative importance. Citation: Paap T, Marincowitz S, Pham NQ, Roets F, Basson RJ, Wingfield BD, Oberlander K, Wingfield MJ (2023). A novel species of Microsphaeropsis causing cankers on Rafnia amplexicaulis in South Africa. Fungal Systematics and Evolution 12: 73-80. doi: 10.3114/fuse.2023.12.05.