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1.
Rev Epidemiol Sante Publique ; 67(5): 295-301, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31288955

RESUMO

BACKGROUND: University students are subject to stress due to academic pressure, empowerment and transition from adolescence to adulthood. This young population may have a higher risk of functional disorders as eating disorders (ED) and irritable bowel syndrome (IBS). Our objective was to determine the prevalence of ED, IBS and both and the associated behaviours. METHODS: A cross sectional study was conducted in Rouen University (France). Participating students filled an anonymous self-questionnaire with items on socio-demographics, depression (Duke score), stress (Cohen score), emotional exhaustion (Maslach Inventory), insomnia (Insomnia Severity Index), cyberaddiction (Internet Addiction Test), ED (SCOFF-F test) and IBS (Rome III). RESULTS: This study included 731 students (male/female ratio=0.43). The prevalences of ED, IBS and co-existing ED-IBS were respectively 16.7%, 7.8% and 2.7%. ED and IBS were more common in female students. Depression, stress, emotional exhaustion, insomnia and cyberaddiction were significantly associated with ED and IBS or both. Students with ED had a higher risk of having IBS (Adjusted Odds Ratio (AOR)=2.42, 95% CI: 1.30-4.51), and conversely students with IBS had a higher risk of having ED (AOR=2.46, 95% CI: 1.32-4.55) and were more likely to be in the third year of academic study or above (AOR=2.95, 95% CI: 1.50-5.76). CONCLUSION: Students (female especially) suffer from ED and IBS, with a significant risk of co-existing ED-IBS. ED and IBS are related to multiple mental health symptoms, which could lead to negative academic consequences. Screening, using simple and quick tests as SCOFF questionnaire and ROME IV criteria (update of ROME III in 2016), is essential in this population of university students.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Síndrome do Intestino Irritável/epidemiologia , Saúde Mental/estatística & dados numéricos , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Masculino , Prevalência , Estresse Psicológico/complicações , Estresse Psicológico/epidemiologia , Universidades/estatística & dados numéricos , Adulto Jovem
2.
J Evol Biol ; 30(9): 1644-1657, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28379613

RESUMO

Species radiations may be facilitated by phenotypic differences already present within populations, such as those arising through sex-specific development or developmental processes biased towards particular reproductive or trophic morphs. We sought to test this hypothesis by utilizing a comparative transcriptomic approach to contrast among- and within-species differentiation using three horned beetle species in the genus Onthophagus. These three species exhibit differences along three phenotypic axes reflective of much of the interspecific diversity present within the genus: horn location, polarity of sexual dimorphism and degree of nutritional sensitivity. Our approach combined de novo transcript assembly, assessment of amino acid substitutions (dN/dS) across orthologous gene pairs and integration of gene function and conditional gene expression data. We identified 17 genes across the three species pairs related to axis patterning, development and metabolism with dN/dS > 1 and detected elevated dN/dS in genes related to metabolism and biosynthesis in the most closely related species pair, which is characterized by a loss of nutritional polyphenism and a reversal of sexual dimorphism. Further, we found that genes that are conditionally expressed (i.e. as a function of sex, nutrition or body region) within one of our focal species also showed significantly stronger signals of positive or relaxed purifying selection between species divergent along the same morphological axis (i.e. polarity of sexual dimorphism, degree of nutritional sensitivity or location of horns). Our findings thus reveal a positive relationship between intraspecific differentiation due to condition-specific development and genetic divergences among species.


Assuntos
Besouros , Caracteres Sexuais , Transcriptoma , Animais , Feminino , Cornos , Masculino , Fenótipo
3.
Rev Sci Tech ; 35(1): 43-52, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27217167

RESUMO

Viral genome sequencing has become the cornerstone of almost all aspects of virology. In particular, high-throughput, next-generation viral genome sequencing has become an integral part of molecular epidemiological investigations into outbreaks of viral disease, such as the recent outbreaks of Middle Eastern respiratory syndrome, Ebola virus disease and Zika virus infection. Multiple institutes have acquired the expertise and necessary infrastructure to perform such investigations, as evidenced by the accumulation of thousands of novel viral sequences over progressively shorter time periods. The authors recently proposed a nomenclature comprised of five high-throughput sequencing standard categories to describe the quality of determined viral genome sequences. These five categories (standard draft, high quality, coding complete, complete and finished) cover all levels of viral genome finishing and can be applied to sequences determined by any technology platform or assembly technique.


Le séquençage des génomes viraux est devenu la pierre angulaire de pratiquement toutes les facettes de la virologie. En particulier, le séquençage à haut débit de nouvelle génération est désormais une partie intégrante des enquêtes d'épidémiologie moléculaire relatives aux foyers de maladies virales, par exemple les récentes épidémies du syndrome respiratoire du Moyen-Orient, la maladie due au virus Ebola ou l'infection par le virus Zika. Nombre d'institutions ont acquis les compétences techniques et les infrastructures nécessaires pour réaliser ce type d'enquêtes, comme en témoigne l'accumulation de milliers de séquences virales nouvelles obtenues en un laps de temps de plus en plus court. Les auteurs ont récemment élaboré une nomenclature constituée de cinq catégories de référence décrivant la qualité des séquences d'un génome viral obtenues par séquençage à haut débit. Ces cinq catégories (ébauche de référence, séquence de haute qualité, séquence codante complète, séquence complète et séquence finie) couvrent toutes les étapes de la finition du génome viral et s'appliquent quelle que soit la plateforme technologique ou la technique d'assemblage utilisée pour déterminer la séquence.


La secuenciación del genoma vírico se ha erigido a día de hoy en la piedra angular de casi todos los aspectos de la virología. La secuenciación de alto rendimiento de próxima generación, en particular, es ahora un componente integral de las investigaciones de epidemiología molecular sobre brotes de enfermedades víricas como los registrados últimamente de síndrome respiratorio de Oriente Medio, enfermedad por el virus del Ebola o infección por el virus Zika. Numerosas instituciones se han dotado de las competencias técnicas y la infraestructura necesaria para llevar a cabo tales investigaciones, como deja patente la acumulación de miles de nuevas secuencias víricas en periodos de tiempo cada vez más cortos. En fechas recientes los autores han propuesto una nomenclatura compuesta de cinco categorías de referencia que sirven para describir la calidad de las secuencias de genoma vírico determinadas por secuenciación de alto rendimiento. Estas cinco categorías (borrador normal, gran calidad, codificación completa, completa y acabada) cubren toda la gradación de acabados en la secuenciación de genoma vírico y pueden ser aplicadas a las secuencias obtenidas por cualquier dispositivo técnico o cualquier técnica de ensamblaje.


Assuntos
Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Vírus/genética , Animais , Sequenciamento de Nucleotídeos em Larga Escala/classificação , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Epidemiologia Molecular , Terminologia como Assunto , Viroses/epidemiologia , Viroses/veterinária , Viroses/virologia
4.
Odontostomatol Trop ; 39(156): 49-56, 2016 Dec.
Artigo em Francês | MEDLINE | ID: mdl-30240551

RESUMO

Objective: The aim of the study was to investigate oral health in asthmatic children using inhaled therapy and to compare the oral health status according to ß2 agonist and corticosteroid dose administrated. Methods: The study group composed of 160 children aged between 2 and 15 years old who had bronchial asthma at different degrees of severity, the children followed at university hospital of Casablanca. A questionnaire was filled referring to oral health habits. For dental examinations, world health organization criteria and for plaque indices the Silness and Löe plaque index were used. Oral mucosal was examined to detect candidiasis or ulcerations. Results: The dental plaque registered was 1,13 ± 0,64. The mean DMFT was 3,75 ± 1,53 and the mean DMFT was 5,50 ± 3,02. A statistically significant higher average DMFT and DMFT values were observed with higher dose of ß2 agonist (p < 0,05). Almost a third of studied population had oral candidiasis and 6,9% had ulcerations. These oral mucosal lesions were particularly observed in children receiving inhaled corticosteroid higher than 400 µg/j (P < 10-5) and they were lower in children using a spacer device and rinsing the mouth after treatment (P < 10-5). Conclusion: The results suggest higher caries susceptibility and oral mucosal lesions among asthmatic children undergoing inhaled treatment with ß2 agonist and corticosteroid. A special attention by doctors and health professionals of these patients is necessary and asthmatic children are recommended to adopt more precautionary oral hygiene practices.


Assuntos
Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Suscetibilidade à Cárie Dentária , Saúde Bucal , Administração por Inalação , Adolescente , Corticosteroides/administração & dosagem , Agonistas Adrenérgicos beta/administração & dosagem , Criança , Pré-Escolar , Índice CPO , Índice de Placa Dentária , Feminino , Humanos , Lactente , Masculino , Marrocos , Fatores de Risco , Inquéritos e Questionários
5.
Rev Epidemiol Sante Publique ; 62(1): 33-40, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24434248

RESUMO

BACKGROUND: Publications are the primary output of scientific research. We conducted a national study to quantify Algerian medical teachers' research output and identify its determinants during the 2000-2009 decade. METHODS: The American Medline database and the French Pascal database were used. A publication was eligible only if the lead author was an Algerian medical teacher (in medicine, pharmacy, or dentistry) working in Algeria. The same questionnaire was completed by cases (teachers who were first authors of an original article during the study period) and randomly selected controls. Logistic regression analysis was used to identify factors related to research output. RESULTS: A total of 79 original articles (42.2% of publications) were retrieved, a quarter of which were listed in Pascal alone. The publication rate was 2.6 original articles per 1000 teachers per year. The journals that published these original articles had a median impact factor of 0.83. The ability to publish an original article was 4.3 times higher if the teacher had undergone training in biostatistics and/or epidemiology (adjusted odds ratio [aOR]=4.31, 95% confidence interval [CI]: 1.79-10.38). A promotion evaluation grid that did not encourage writing (aOR=3.44, 95% CI: 1.42-8.33), a doctoral thesis, seniority, foreign collaboration, and English language proficiency were found to be associated with publication output. CONCLUSIONS: Algerian medical teachers' research output was particularly low. Replacing the current promotion grid with a grid that promotes writing, developing abilities to read and write articles and developing English language proficiency are likely to improve this situation.


Assuntos
Pesquisa Biomédica/estatística & dados numéricos , Docentes , Publicações/estatística & dados numéricos , Faculdades de Medicina , Adulto , Argélia , Pesquisa Biomédica/tendências , Docentes/estatística & dados numéricos , Feminino , Humanos , Fator de Impacto de Revistas , Idioma , Masculino , Pessoa de Meia-Idade , Editoração/estatística & dados numéricos , Faculdades de Medicina/estatística & dados numéricos , Recursos Humanos , Carga de Trabalho/estatística & dados numéricos
6.
Occup Med (Lond) ; 63(7): 473-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23925975

RESUMO

BACKGROUND: Data about perceived needs of workers for information on occupational hazards or diseases (OHDs) are scarce and the behaviour of workers seeking information on these matters is not well known. AIMS: To describe workers' needs and behaviour in seeking information about OHDs. METHODS: All workers attending for consultation at an occupational health service in Upper Normandy within 1 week were invited to fill in an anonymous questionnaire. RESULTS: Of the 2640 workers responding 58% declared a need for information about OHD, but only 37% actually sought that information. Whereas 82% of workers mentioned the internet and their general physician (GP) as sources of information on OHD, only 43% mentioned their occupational physician (OP). Furthermore, information received from OPs was not considered more reliable than that from GPs. CONCLUSIONS: Workers report a need for information about OHDs. Although most of them trust information given by OPs, they do not use OPs to obtain OHD information, but instead use less reliable sources such as the internet or their GPs.


Assuntos
Letramento em Saúde , Comportamento de Busca de Informação , Doenças Profissionais , Serviços de Saúde do Trabalhador , Saúde Ocupacional , Adulto , Feminino , França , Clínicos Gerais , Necessidades e Demandas de Serviços de Saúde , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Inquéritos e Questionários , Confiança
7.
SSM Popul Health ; 16: 100936, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34611543

RESUMO

Higher-education students face substantial risks for developing depressive symptoms during the COVID-19 pandemic or experiencing exacerbated pre-existing depressive symptoms. This study uses data from the COVID-19 International Student Well-Being Study, which collected data through a non-representative convenience sample in 125 higher-education institutions (HEI) across 26 high- and middle-income countries (N: 20,103) during the first wave of the COVID-19 pandemic. It describes the prevalence of depressive symptoms in higher-education students. We find substantial cross-national variation in depressive symptoms, with lowest mean levels established in the Nordic countries and France, while highest mean levels of depressive symptoms were found in Turkey, South Africa, Spain and the USA. Elevated risk for depressive symptoms was found in female students, students with fewer social support resources and in a more disadvantaged socioeconomic position, and students with a migrant background. COVID-19 related stressors, such as reduced social contact, increased financial insecurity, and academic stress explained a relatively larger proportion of the variance in depressive symptoms compared to non-COVID-19 related stressors. This finding shows that not the pandemic itself, but rather the secondary effects of the pandemic relate to students' mental health. Our results enable HEIs to be better equipped to target groups that are particularly at risk during a pandemic.

9.
Proteins ; 72(2): 761-8, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18260113

RESUMO

In ColE1, the plasmid encoded RNA one modulator (Rom) protein, which is also referred to as Rop, specifically binds and stabilizes an intermediate RNA loop-loop kissing structure formed between the plasmid encoded transcripts RNA I and RNA II and thereby acts as an auxiliary repressor of replication. Rom folds into a homodimeric, cylindrically packed four helix bundle with an exact twofold symmetry axis (Banner et al., J Mol Biol 1987;196:657-675; Eberle et al., J Biomol 1991;1:71-83). Previous studies (Castagnoli et al., EMBO J 1989;8:621-629; Predki et al., Cell 1995;80:41-50) have localized the RNA binding surface to the H1/H1' face of the helical bundle and found Phe14 to be a key determinant of the binding affinity and specificity for RNA kissing complexes. To investigate the role of Phe14 in RNA recognition, we have determined high-resolution crystal structures of two point mutants of Rom (F14Y and F14W), as well as a high-resolution structure of a crystal form of Rom in which the dimer comprises the asymmetric unit. Although the structures of F14Y and F14W share a very high degree of structural identity with that of the wild-type protein and each other, differences are observed between the three polypeptide chains found in the asymmetric unit of each crystal in the packing of the tryptophan and tyrosine side chains at position 14, as well as some of the other surface exposed side chains of key amino acids involved in RNA binding. In both the wild-type Rom and mutant structures, crystal packing forces can break the exact twofold symmetry of the dimer and influence the conformation of the side chains presented on the H1/H1' face of Rom. Since the new structures show such a high degree of structural identity, the disruption in RNA binding observed for the mutant proteins can be attributed specifically to the chemical nature of the side chain at position 14. Moreover, the fact that even subtle changes in the side chain at position 14 cannot be compensated for by the apparent flexibility of this side chain suggests a highly constrained packing of this residue in the RNA-protein complex.


Assuntos
Proteínas de Bactérias/química , RNA/química , Cristalografia por Raios X , Conformação Proteica
10.
PLoS One ; 13(3): e0194188, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29566003

RESUMO

BACKGROUND: Healthcare students are future health care providers and serve as role models and coaches to enhance behaviors for healthy lifestyles. However healthcare students face multiple stressors that could lead to adopting risk behaviors. OBJECTIVES: To assess the changes in health risk factors among healthcare students between 2007 and 2015, and to identify specific health behaviors based on the curriculum in a population of healthcare students. METHODS: Two cross sectionnal studies were conducted in 2007 and 2015 among nursing, medical, pharmacy, and physiotherapy students (Rouen, France). During compulsory courses and examination sessions students filled self-administered questionnaires on socio-demographic characteristics and behavior as: tobacco smoking, alcohol consumption, cannabis consumption, eating disorders, regular practice of sport, perceived health, stress and use of psychotropic drugs. RESULTS: 2,605 healthcare students were included (1,326 in 2007 and 1,279 in 2015), comprising 1,225 medical students (47.0%), 738 nursing students (28.3%), 362 pharmacy students (13.9%), and 280 physiotherapy students (10.8%). Between 2007 and 2015, occasional binge drinking and regular practice of sport increased significantly among healthcare students, respectively AOR = 1.48 CI95% (1.20-1.83) and AOR = 1.33 CI95% (1.11-1.60), regular cannabis consumption decreased significantly, AOR = 0.32 CI95% (0.19-0.54). There was no change in smoking or overweight/obese. There was a higher risk of frequent binge drinking and a lower risk of tobacco smoking in all curricula than in nursing students. Medical students practiced sport on a more regular basis, were less overweight/obese, had fewer eating disorders than nursing students. CONCLUSION: Our findings demonstrate a stable frequency of classic behaviors as smoking but a worsening of emerging behaviors as binge drinking among healthcare students between 2007 and 2015. Health behaviors differed according to healthcare curricula and nursing students demonstrated higher risks. As health behaviors are positively related to favorable attitudes towards preventive counseling, therefore healthcare students should receive training in preventive counseling and develop healthy lifestyles targeted according to the health curriculum.


Assuntos
Atitude Frente a Saúde , Educação de Graduação em Medicina , Comportamentos Relacionados com a Saúde , Inquéritos e Questionários , Adulto , Estudos Transversais , Feminino , Humanos , Masculino
11.
Curr Opin Struct Biol ; 6(5): 595-603, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8913680

RESUMO

Advances in the crystallization of biological macromolecules have come not only from the application of biochemical, molecular biological and immunological principles and techniques, but also from continued efforts to understand the crystallization process. Developments in crystallization methodologies, protocols, and reagents are also facilitating crystallization efforts.


Assuntos
Cristalografia por Raios X , Substâncias Macromoleculares , Animais , Cristalização , Humanos
12.
Nat Biotechnol ; 17(3): 265-70, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10096294

RESUMO

Several nonmammalian members of the RNase A superfamily exhibit anticancer activity that appears to correlate with resistance to the cytosolic ribonuclease inhibitor (RI). We mutated two human ribonucleases-pancreatic RNase (hRNAse) and eosinophil-derived neurotoxin (EDN)-to incorporate cysteine residues at putative sites of close contact to RI, but distant from the catalytic sites. Coupling of Cys89 of RNase and Cys87 of EDN to proteins at these sites via a thioether bond produced enzymatically active conjugates that were resistant to RI. To elicit cellular targeting as well as to block RI binding, transferrin was conjugated to a mutant human RNase, rhRNase(Gly89)-->Cys) and a mutant EDN (Thr87-->Cys). The transferrin-rhRNase(Gly89-->Cys) thioether conjugate was 5000-fold more toxic to U251 cells than recombinant wild-type hRNase. In addition, transferrin-targeted EDN exhibited tumor cell toxicities similar to those of hRNase. Thus, we endowed two human RI-sensitive RNases with greater cytotoxicity by increasing their resistance to RI. This strategy has the potential to generate a novel set of recombinant human proteins useful for targeted therapy of cancer.


Assuntos
Proteínas/genética , Ribonuclease Pancreático/genética , Ribonucleases/antagonistas & inibidores , Animais , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Neurotoxina Derivada de Eosinófilo , Glioma/metabolismo , Humanos , Concentração Inibidora 50 , Cinética , Leucina/metabolismo , Modelos Moleculares , Mutagênese Sítio-Dirigida , Plasmídeos , Engenharia de Proteínas , Proteínas/farmacologia , Receptores da Transferrina/imunologia , Proteínas Recombinantes/metabolismo , Ribonuclease Pancreático/farmacologia , Suínos , Transferrina/uso terapêutico , Células Tumorais Cultivadas
14.
PLoS One ; 12(2): e0171363, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28187198

RESUMO

Burkholderia pseudomallei (Bp), the agent of melioidosis, causes disease ranging from acute and rapidly fatal to protracted and chronic. Bp is highly infectious by aerosol, can cause severe disease with nonspecific symptoms, and is naturally resistant to multiple antibiotics. However, no vaccine exists. Unlike many Bp strains, which exhibit random variability in traits such as colony morphology, Bp strain MSHR5848 exhibited two distinct and relatively stable colony morphologies on sheep blood agar plates: a smooth, glossy, pale yellow colony and a flat, rough, white colony. Passage of the two variants, designated "Smooth" and "Rough", under standard laboratory conditions produced cultures composed of > 99.9% of the single corresponding type; however, both could switch to the other type at different frequencies when incubated in certain nutritionally stringent or stressful growth conditions. These MSHR5848 derivatives were extensively characterized to identify variant-associated differences. Microscopic and colony morphology differences on six differential media were observed and only the Rough variant metabolized sugars in selective agar. Antimicrobial susceptibilities and lipopolysaccharide (LPS) features were characterized and phenotype microarray profiles revealed distinct metabolic and susceptibility disparities between the variants. Results using the phenotype microarray system narrowed the 1,920 substrates to a subset which differentiated the two variants. Smooth grew more rapidly in vitro than Rough, yet the latter exhibited a nearly 10-fold lower lethal dose for mice than Smooth. Finally, the Smooth variant was phagocytosed and replicated to a greater extent and was more cytotoxic than Rough in macrophages. In contrast, multiple locus sequence type (MLST) analysis, ribotyping, and whole genome sequence analysis demonstrated the variants' genetic conservation; only a single consistent genetic difference between the two was identified for further study. These distinct differences shown by two variants of a Bp strain will be leveraged to better understand the mechanism of Bp phenotypic variability and to possibly identify in vitro markers of infection.


Assuntos
Burkholderia pseudomallei/genética , Genes Bacterianos , Fenótipo , Polimorfismo Genético , Animais , Burkholderia pseudomallei/patogenicidade , Linhagem Celular , Farmacorresistência Bacteriana/genética , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Virulência/genética
15.
Genome Announc ; 4(1)2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26744368

RESUMO

Burkholderia mallei, the etiologic agent of glanders, is a Gram-negative, nonmotile, facultative intracellular pathogen. Although glanders has been eradicated from many parts of the world, the threat of B. mallei being used as a weapon is very real. Here we present draft genome assemblies of 8 Burkholderia mallei strains that were isolated in Turkey.

16.
Genome Announc ; 4(3)2016 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-27174274

RESUMO

Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, Zika virus/Homo sapiens-tc/THA/2014/SV0127-14 and Zika virus/H. sapiens-tc/PHL/2012/CPC-0740, isolated from the blood of patients collected in Thailand, 2014, and the Philippines, 2012, respectively. Sequencing and phylogenetic analysis showed that both strains belong to the Asian lineage.

17.
J Mol Biol ; 257(5): 992-1007, 1996 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-8632481

RESUMO

A number of biochemical properties differ dramatically among homologues within the pancreatic ribonuclease superfamily. Human pancreatic ribonuclease (hRNase) has high enzyme activity, extreme sensitivity to ribonuclease inhibitor (RI) and is non-toxic, whereas a homologous RNase from frog eggs, called onconase, has much lower enzyme activity, is not sensitive to RI and is cytotoxic to cancer cell lines and animals. To explore the structural basis of these differences among members in the RNAse family we synthesized genes for onconase, hRNase, a mutant onconase (K9Q) and onconase-hRNase N-terminal hybrids and expressed the proteins in Escherichia coli with final yields of 10 to 50 mg per liter of culture after purification. A recombinant version of onconase with an N-terminal methionine instead of the native pyroglutamyl residue had decreased cytotoxicity and enzyme activity. Cleavage of the recombinant onconase Met-1 residue, and cyclization of the Gln1 residue to reform the pyroglutamyl N terminus, reconstituted cytotoxicity and enzyme activity. Thus a unique role of the pyroglutamyl residue in the active site of amphibian RNases is indicated. Replacement of one to nine residues of onconase with the homologous residues of hRNase increased the enzymatic activity against most of the substrates tested with a simultaneous shift in the enzyme specificity from high preference for poly(U) to slight preference for poly(C). Cytotoxicity of the chimera decreased, dissociating cytotoxicity from enzymatic activity. The molecular basis for the low binding affinity of onconase for RI has been examined experimentally with the recombinant RNases and by fitting onconase and RNase A structures to the coordinates from the recently published RNase A-RI complex.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Proteínas do Ovo/metabolismo , Inibidores Enzimáticos/farmacologia , Hormônios Placentários/farmacologia , Ribonuclease Pancreático/metabolismo , Ribonucleases/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Proteínas do Ovo/antagonistas & inibidores , Proteínas do Ovo/química , Proteínas do Ovo/farmacologia , Humanos , Cinética , Dados de Sequência Molecular , Mutagênese , Concentração Osmolar , Ácido Pirrolidonocarboxílico/química , Ácido Pirrolidonocarboxílico/metabolismo , RNA/metabolismo , Rana pipiens , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Ribonuclease Pancreático/antagonistas & inibidores , Ribonuclease Pancreático/química , Ribonuclease Pancreático/farmacologia , Ribonucleases/antagonistas & inibidores , Ribonucleases/química , Ribonucleases/farmacologia , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , Células Tumorais Cultivadas
18.
AIDS ; 10(1): 69-75, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8924254

RESUMO

OBJECTIVE: To identify factors associated with failure to return for HIV post-test counselling in pregnant women in Kigali (Rwanda). SUBJECTS AND METHODS: In the context of a study on the impact of HIV infection on pregnancy, HIV-1-antibody testing was offered to all pregnant women attending the antenatal clinic of the Centre Hospitalier de Kigali from July 1992 to August 1993. Pre-test counselling was performed after verbal informed consent was obtained. Two weeks later, we formally enrolled all HIV-positive women and a corresponding number of HIV-negative women in a cohort. At this visit, post-test counselling was given to those wishing to be informed of their HIV serostatus. Level of knowledge about modes of HIV transmission and condom use were recorded. Four months after delivery, another interview was conducted to determine the proportion of women who used condoms regularly. RESULTS: A total of 1233 pregnant women were screened. The HIV seroprevalence was 34.4% [95% confidence interval (CI), 31.7-37.1]; 271 (63.9%) out of 424 HIV-positive and 577 (71.3%) out of 809 HIV-negative women asked for their HIV serostatus (P = 0.008). In multivariate analysis, the only variable significantly associated with failure to return for post-test counselling was a positive HIV test result (odds ratio, 0.7; 95% CI, 0.5-0.9; P = 0.009), independently of obstetrical history and socioeconomic characteristics. Among the 848 women who had post-test counselling, 50.9% of the HIV-positive women and 94.6% of the HIV-negative women stated that they planned to inform their partner of their serostatus (P = 0.0001). More than 95% of the women interviewed knew about sexual and parenteral transmission of HIV, but half were unaware of mother-to-child transmission. More than 80% of the women had seen a condom before, but 14% only had used it at least once. Among women who were sexually active 4 months after delivery, 8.8% of the HIV-positive and 3.9% of the HIV-negative women reported using a condom (P = 0.04). CONCLUSION: Innovative approaches for HIV testing and counselling programs are needed and the importance of psychosocial and cultural factors associated with HIV testing should be emphasized in African populations.


Assuntos
Aconselhamento , Soropositividade para HIV/psicologia , Cooperação do Paciente , Complicações Infecciosas na Gravidez/psicologia , Sorodiagnóstico da AIDS , Adolescente , Adulto , Estudos de Coortes , Escolaridade , Feminino , Soropositividade para HIV/diagnóstico , Humanos , Estado Civil , Ocupações , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Ruanda , Parceiros Sexuais
19.
AIDS ; 12(6): 643-50, 1998 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-9583605

RESUMO

OBJECTIVE: To study the effect of HIV-1 infection on pregnancy outcome in women provided with antenatal services including malaria and sexually transmitted disease (STD) treatment in Kigali, Rwanda. SUBJECTS AND METHODS: Pregnant women attending the antenatal clinic ward of the Centre Hospitalier de Kigali in their last 3 months of pregnancy were tested for HIV antibody after consent had been obtained. All HIV-1-infected women were included and compared with HIV-negative women of same age and parity. Until delivery, each woman enrolled had a monthly follow-up including malaria and STD aetiological diagnosis and treatment. At the time of delivery, obstetrical and neonatal characteristics were recorded. Mothers and their children were followed until 6 weeks postpartum. RESULTS: By mid-August 1993, 384 HIV-positive and 381 HIV-negative women had been enrolled and by the end of November 1993, 729 women (95.3%; 364 HIV-positive and 365 HIV-negative) had delivered 725 livebirths, including eight and six twins, respectively; 10 stillbirths were recorded amongst HIV-positive women and eight amongst HIV-negative women (P=0.60). Excluding twins, premature birth (< 37 completed weeks of gestation) was observed in 22.7% of infants born to HIV-positive women versus 14.1% of those born to HIV-negative women; low birth weight (< 2500 g) was observed in 25.5% of infants born to HIV-positive women versus 14.8% of those born to HIV-negative women. Low birth weight was significantly more frequent in full-term infants born to HIV-positive mothers than to HIV-negative mothers. No significant difference in low birth weight rate was observed in preterm infants. Death occurred in 5.1% of children during the perinatal period without statistically significant difference between the two groups. HIV-positive women were more likely to have a postpartum haemorrhage. CONCLUSION: In the context of high HIV prevalence, maternal HIV infection is associated with adverse obstetrical and neonatal outcomes even when treating STD and malaria.


Assuntos
Soropositividade para HIV/complicações , HIV-1 , Complicações Infecciosas na Gravidez , Resultado da Gravidez , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Anticorpos Anti-HIV/sangue , Soronegatividade para HIV , Humanos , Recém-Nascido , Malária/tratamento farmacológico , Período Pós-Parto , Gravidez , Estudos Prospectivos , Fatores de Risco , Ruanda , Infecções Sexualmente Transmissíveis/tratamento farmacológico
20.
Int J Epidemiol ; 27(6): 1072-7, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10024206

RESUMO

OBJECTIVE: To study the relationship between human immunodeficiency virus (HIV) infection and body weight in African women during and after pregnancy. METHODS: A prospective cohort study was initiated at the Centre Hospitalier de Kigali in July 1992. Every woman seen at the antenatal clinic and with a gestational age of <28 weeks was offered HIV-1 antibody testing. Comparable numbers of HIV-infected (HIV+) and uninfected (HIV-) women were recruited. At inclusion, socio-demographic characteristics and self-reported pre-pregnancy weight were recorded; height and weight were measured. Each woman enrolled had a monthly follow-up until 9 months after delivery, with a clinical examination including weighing. Three anthropometric indices were used to answer the study objectives: weight, body mass index (BMI), and pregnancy balance. RESULTS: As of April 1994, 101 HIV+ and 106 HIV- women were followed until 5 months after delivery. Weight and BMI during pregnancy were lower in HIV+ women than in HIV- women. After delivery, weight and BMI gains were significantly lower in HIV+ women. Until 5 months after delivery, the mean weight variation was -2.2 kg (standard deviation [SD] = 5.9 kg) in HIV+ women and +0.2 kg (SD = 6.6 kg) in HIV- women (P = 0.007) in comparison to pre-pregnancy weight. Comparisons of the slopes of the weight curves did not show statistical differences throughout the pregnancy, but it did during the post-partum period (P = 0.02). CONCLUSIONS: Our study suggests that HIV infection could impair nutritional status in pregnant women, especially during the post-partum period. Family planning and maternal and child health services including HIV testing and counselling, should consider a nutritional assessment and intervention programme targeted to HIV+ pregnant women.


Assuntos
Peso Corporal , Infecções por HIV/epidemiologia , HIV-1 , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Índice de Massa Corporal , Feminino , Seguimentos , Anticorpos Anti-HIV/análise , HIV-1/imunologia , Humanos , Incidência , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Ruanda/epidemiologia , Inquéritos e Questionários
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