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1.
EMBO J ; 36(21): 3212-3231, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-28982779

RESUMO

Nuclear actin regulates transcriptional programmes in a manner dependent on its levels and polymerisation state. This dynamics is determined by the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation. Here, using Xenopus egg extracts and human somatic cells, we show that actin dynamics and formins are essential for DNA replication. In proliferating cells, formin inhibition abolishes nuclear transport and initiation of DNA replication, as well as general transcription. In replicating nuclei from transcriptionally silent Xenopus egg extracts, we identified numerous actin regulators, and disruption of actin dynamics abrogates nuclear transport, preventing NLS (nuclear localisation signal)-cargo release from RanGTP-importin complexes. Nuclear formin activity is further required to promote loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin, as well as initiation and elongation of DNA replication. Therefore, actin dynamics and formins control DNA replication by multiple direct and indirect mechanisms.


Assuntos
Actinas/genética , Cromatina/metabolismo , Replicação do DNA , Proteínas Fetais/genética , Proteínas dos Microfilamentos/genética , Proteínas Nucleares/genética , Transcrição Gênica , Actinas/metabolismo , Transporte Ativo do Núcleo Celular/genética , Animais , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Cromatina/química , Misturas Complexas/química , Citoplasma/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Proteínas Fetais/metabolismo , Forminas , Regulação da Expressão Gênica , Células HeLa , Humanos , Carioferinas/genética , Carioferinas/metabolismo , Proteínas dos Microfilamentos/metabolismo , Sinais de Localização Nuclear , Proteínas Nucleares/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Transdução de Sinais , Xenopus laevis , Zigoto/química , Proteína ran de Ligação ao GTP/genética , Proteína ran de Ligação ao GTP/metabolismo
2.
Cell Microbiol ; 20(4)2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29084417

RESUMO

The infection of the model legume Medicago truncatula with Ralstonia solanacearum GMI1000 gives rise to bacterial wilt disease via colonisation of roots. The root and leaf responses to early infection (1 and 3 days post infection) were characterised to investigate the molecular mechanisms of plant resistance or susceptibility. A proteomics approach based on pools of susceptible and resistant recombinant inbred lines was used to specifically target the mechanisms for tolerance. Differential abundances were evidenced for proteins involved in defence (e.g., PR5, PR10, or Kunitz protease inhibitors) and signalling pathways (such as cyclophilin). R. solanacearum inoculation modifies expression levels of those genes, either in both genotypes (AOS1, LOX4, and proteinase inhibitors) or specifically in the resistant line (PR proteins). Exogenous application of salicylic acid (SA) enhanced tolerance to the bacteria, whereas methyl jasmonate (MeJA) enhanced short-term tolerance then promoted disease in the susceptible ecotype, suggesting that they may mediate defence responses. Conversely, proteomics-identified genes were also shown to be SA or MeJA responsive. This is the first description of differential response to R. solanacearum in M. truncatula. Our results suggest that root basal defence is activated at 1 dpi, together with the JA pathway. Specific resistance is then evidenced at three dpi, with the up-regulation of SA-dependent PR proteins.


Assuntos
Medicago truncatula/metabolismo , Medicago truncatula/microbiologia , Doenças das Plantas/microbiologia , Ralstonia solanacearum , Acetatos/farmacologia , Ciclopentanos/farmacologia , Medicago truncatula/genética , Oxilipinas/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Proteômica , Ácido Salicílico/farmacologia
3.
Mol Cell ; 44(3): 437-50, 2011 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-22055189

RESUMO

Bistability of the Cdk1-Wee1-Cdc25 mitotic control network underlies the switch-like transitions between interphase and mitosis. Here, we show by mathematical modeling and experiments in Xenopus egg extracts that protein phosphatase 2A (PP2A), which can dephosphorylate Cdk1 substrates, is essential for this bistability. PP2A inhibition in early interphase abolishes the switch-like response of the system to Cdk1 activity, promoting mitotic onset even with very low levels of Cyclin, Cdk1, and Cdc25, while simultaneously inhibiting DNA replication. Furthermore, even if replication has already initiated, it cannot continue in mitosis. Exclusivity of S and M phases does not depend on bistability only, since partial PP2A inhibition prevents replication without inducing mitotic onset. In these conditions, interphase-level mitotic kinases inhibit Cyclin E-Cdk2 chromatin loading, blocking initiation complex formation. Therefore, by counteracting both Cdk1 activation and activity of mitotic kinases, PP2A ensures robust separation of S phase and mitosis and dynamic transitions between the two states.


Assuntos
Pontos de Checagem da Fase M do Ciclo Celular , Proteína Fosfatase 2/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular , Proteínas de Xenopus/metabolismo , Animais , Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular/metabolismo , Montagem e Desmontagem da Cromatina , Simulação por Computador , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Replicação do DNA , Inibidores Enzimáticos/farmacologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Modelos Biológicos , Análise Numérica Assistida por Computador , Fosforilação , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2/genética , Proteínas Tirosina Quinases/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Fatores de Tempo , Xenopus , Proteínas de Xenopus/antagonistas & inibidores , Proteínas de Xenopus/genética , Fosfatases cdc25/metabolismo
4.
Fam Pract ; 35(4): 376-382, 2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-29267889

RESUMO

Background: Number of patients needed to treat (NNT) with a statin in primary prevention of coronary heart disease (CHD) is often misinterpreted because this single statistic averages results from heterogeneous studies. Objective: To provide estimates of the number of individuals needed to be prescribed a statin to prevent one CHD event accounting for their level of CHD risk and for persistence to treatment. Methods: A post hoc analysis was conducted based on a Cochrane review on statins for the primary prevention of cardiovascular diseases. Five-year NNTs were calculated separately from randomized clinical trials (RCTs), including 'lower' and 'higher' risk populations (CHD mean event rates of 3.7 and 14.4 per 1000 person-years, respectively). NNTs were adjusted for 5-year persistence to treatment using a value of 65%. Results: Persistence-adjusted 5-year NNTs to prevent one CHD for the lower and higher CHD risk categories were 146 [95% confidence interval (CI): 117-211] and 53 (95% CI: 39-88) respectively, values 25% and 15% higher than their unadjusted counterpart (117, 95% CI: 94-167 and 46, 95% CI: 34-78). Conclusions: Five-year NNTs for statins to prevent a first CHD is almost three times higher in those at lower versus higher risk populations. Reporting combined results from RCTs including subjects at different cardiovascular risks should be avoided. Individualizing the risk of CHD should orient family physicians and their patients in their choice of preventive approaches and generate more realistic expectations about compliance and outcomes.


Assuntos
Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prevenção Primária , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
5.
J Interprof Care ; 32(4): 525-528, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29589780

RESUMO

In the last decades, interactions between health professionals have mostly been discussed in the context of interprofessional teamwork where professionals work closely together and share a team identity. Comparatively, little work has been done to explore interactions that occur between professionals in contexts where traditionally formal structures have been less supporting the implementation of interprofessional teamwork, such as in the private healthcare sector. The objective of this study was to identify private sector physiotherapists' perceptions of interprofessional and intraprofessional work regarding interventions for adults with low back pain. This was a cross-sectional survey of 327 randomly-selected physiotherapists. Data were analysed using descriptive statistics. A majority of physiotherapists reported positive effects of interprofessional work for their clients, themselves and their workplaces. Proximity of physiotherapists with other professionals, clinical workloads, and client's financial situation were perceived as important factors influencing the implementation of interprofessional work. Low back pain is a highly prevalent and disabling condition. The results of this study indicate that integrating interprofessional work in the management of low back pain in the private sector is warranted. Furthermore, the implementation of interprofessional work is viewed by practicing physiotherapists as dependent upon certain client-, professional- and organizational-level factors.


Assuntos
Atitude do Pessoal de Saúde , Relações Interprofissionais , Dor Lombar/reabilitação , Fisioterapeutas/psicologia , Setor Privado , Adulto , Comportamento Cooperativo , Estudos Transversais , Feminino , Processos Grupais , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/organização & administração , Percepção , Rede Social , Local de Trabalho
6.
J Autoimmun ; 79: 84-90, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28190705

RESUMO

BACKGROUND: Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. OBJECTIVES: To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. METHODS: Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008-2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. RESULTS: With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41-0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. CONCLUSION: Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.


Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Vacinas contra Papillomavirus/efeitos adversos , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Razão de Chances , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vigilância da População , Risco , Adulto Jovem
7.
Am J Public Health ; 107(1): 100-104, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27854518

RESUMO

Enhancing effective preventive interventions to address contemporary public health problems requires improved capacity for applied public health research. A particular need has been recognized for capacity development in population health intervention research to address the complex multidisciplinary challenges of developing, implementing, and evaluating public health practices, intervention programs, and policies. Research training programs need to adapt to these new realities. We have presented an example of a 2003 to 2015 training program in transdisciplinary research on public health interventions that embedded doctoral and postdoctoral trainees in public health organizations in Quebec, Canada. This university-public health partnership for research training is an example of how to link science and practice to meet emerging needs in public health.


Assuntos
Pesquisa Biomédica/educação , Saúde Pública/educação , Parcerias Público-Privadas/organização & administração , Universidades , Currículo , Humanos , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Prática de Saúde Pública , Quebeque , Critérios de Admissão Escolar , Apoio ao Desenvolvimento de Recursos Humanos
8.
Pharmacoepidemiol Drug Saf ; 26(3): 239-247, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28052554

RESUMO

PURPOSE: Randomized-controlled trials and claims databases suggest that antiepileptic drug (AED) use may increase the risk of suicide attempts (SA). The present case-control study explores the impact of underlying indications on this potential association. METHODS: Physicians collected the medical history; prior 12-month drug use was obtained from standardized telephone interviews with patients. The association between AED use and SA was explored using multivariate conditional logistic regression. The analyses were replicated after stratification on depression and neurological disorders (epilepsy, migraine, and chronic neuropathic pain). RESULTS: Between 2008 and 2012, 506 adults with an incident SA were recruited in suicide treatment centers from across France and socio-demographically matched to 2829 controls from primary care settings. The association between AED use and odds of SA was not significant overall (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.9-2.4). No association was observed for patients with neurological disorders (OR, 1.1; 95%CI, 0.5-2.4) as opposed to patients with depression (OR, 1.6; 95%CI, 1.0-2.5), but unmeasured confounding was suspected. CONCLUSIONS: Our results suggest that the association observed between AED use and increased odds of non-fatal SA in patients with either a lifetime history of depression or no neurological disorder may be explained by the presence of an underlying psychiatric disorder. Accounting for underlying indications is crucial in drug safety studies, as these can cause a reported association (or lack thereof) to be misleading. This may require the prospective collection of medical data at a patient level. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Anticonvulsivantes/administração & dosagem , Depressão/complicações , Doenças do Sistema Nervoso/complicações , Tentativa de Suicídio/estatística & dados numéricos , Adulto , Anticonvulsivantes/efeitos adversos , Estudos de Casos e Controles , Fatores de Confusão Epidemiológicos , Depressão/tratamento farmacológico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doenças do Sistema Nervoso/tratamento farmacológico , Estudos Prospectivos
9.
Value Health ; 19(1): 75-81, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26797239

RESUMO

BACKGROUND: The concept of the "efficacy-effectiveness gap" (EEG) has started to challenge confidence in decisions made for drugs when based on randomized controlled trials alone. Launched by the Innovative Medicines Initiative, the GetReal project aims to improve understanding of how to reconcile evidence to support efficacy and effectiveness and at proposing operational solutions. OBJECTIVES: The objectives of the present narrative review were 1) to understand the historical background in which the concept of the EEG has emerged and 2) to describe the conceptualization of EEG. METHODS: A focused literature review was conducted across the gray literature and articles published in English reporting insights on the EEG concept. The identification of different "paradigms" was performed by simple inductive analysis of the documents' content. RESULTS: The literature on the EEG falls into three major paradigms, in which EEG is related to 1) real-life characteristics of the health care system; 2) the method used to measure the drug's effect; and 3) a complex interaction between the drug's biological effect and contextual factors. CONCLUSIONS: The third paradigm provides an opportunity to look beyond any dichotomy between "standardized" versus "real-life" characteristics of the health care system and study designs. Namely, future research will determine whether the identification of these contextual factors can help to best design randomized controlled trials that provide better estimates of drugs' effectiveness.


Assuntos
Ensaios Clínicos como Assunto , Tratamento Farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Vigilância de Produtos Comercializados , Resultado do Tratamento , Humanos
10.
BMC Complement Altern Med ; 16: 125, 2016 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-27145957

RESUMO

BACKGROUND: The purpose of the study was to compare utilization of conventional psychotropic drugs among patients seeking care for anxiety and depression disorders (ADDs) from general practitioners (GPs) who strictly prescribe conventional medicines (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHODS: This was one of three epidemiological cohort studies (EPI3) on general practice in France, which included GPs and their patients consulting for ADDs (scoring 9 or more in the Hospital Anxiety and Depression Scale, HADS). Information on all medication utilization was obtained by a standardised telephone interview at inclusion, 1, 3 and 12 months. RESULTS: Of 1562 eligible patients consulting for ADDs, 710 (45.5 %) agreed to participate. Adjusted multivariate analyses showed that GP-Ho and GP-Mx patients were less likely to use psychotropic drugs over 12 months, with Odds ratio (OR) = 0.29; 95 % confidence interval (CI): 0.19 to 0.44, and OR = 0.62; 95 % CI: 0.41 to 0.94 respectively, compared to GP-CM patients. The rate of clinical improvement (HADS <9) was marginally superior for the GP-Ho group as compared to the GP-CM group (OR = 1.70; 95 % CI: 1.00 to 2.87), but not for the GP-Mx group (OR = 1.49; 95 % CI: 0.89 to 2.50). CONCLUSIONS: Patients with ADD, who chose to consult GPs prescribing homeopathy reported less use of psychotropic drugs, and were marginally more likely to experience clinical improvement, than patients managed with conventional care. Results may reflect differences in physicians' management and patients' preferences as well as statistical regression to the mean.


Assuntos
Ansiedade/terapia , Transtorno Depressivo/terapia , Homeopatia , Atenção Primária à Saúde , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicotrópicos/uso terapêutico , Adulto Jovem
11.
Plant Cell Environ ; 38(7): 1312-20, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25366820

RESUMO

The hydraulic conductivity of plant roots (Lp(r)) is determined in large part by the activity of aquaporins. Mechanisms occurring at the post-translational level, in particular phosphorylation of aquaporins of the plasma membrane intrinsic protein 2 (PIP2) subfamily, are thought to be of critical importance for regulating root water transport. However, knowledge of protein kinases and phosphatases acting on aquaporin function is still scarce. In the present work, we investigated the Lp(r) of knockout Arabidopsis plants for four Ca(2+)-dependent protein kinases. cpk7 plants showed a 30% increase in Lp(r) because of a higher aquaporin activity. A quantitative proteomic analysis of wild-type and cpk7 plants revealed that PIP gene expression and PIP protein quantity were not correlated and that CPK7 has no effect on PIP2 phosphorylation. In contrast, CPK7 exerts a negative control on the cellular abundance of PIP1s, which likely accounts for the higher Lp(r) of cpk7. In addition, this study revealed that the cellular amount of a few additional proteins including membrane transporters is controlled by CPK7. The overall work provides evidence for CPK7-dependent stability of specific membrane proteins.


Assuntos
Aquaporinas/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Aquaporinas/genética , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Transporte Biológico , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Mutagênese Insercional , Fosforilação , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Transpiração Vegetal/fisiologia , Plantas Geneticamente Modificadas , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genética , Proteômica , Água/fisiologia
12.
Mol Cell Proteomics ; 12(12): 3886-97, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24056735

RESUMO

In plants, aquaporins play a crucial role in regulating root water transport in response to environmental and physiological cues. Controls achieved at the post-translational level are thought to be of critical importance for regulating aquaporin function. To investigate the general molecular mechanisms involved, we performed, using the model species Arabidopsis, a comprehensive proteomic analysis of root aquaporins in a large set of physiological contexts. We identified nine physiological treatments that modulate root hydraulics in time frames of minutes (NO and H2O2 treatments), hours (mannitol and NaCl treatments, exposure to darkness and reversal with sucrose, phosphate supply to phosphate-starved roots), or days (phosphate or nitrogen starvation). All treatments induced inhibition of root water transport except for sucrose supply to dark-grown plants and phosphate resupply to phosphate-starved plants, which had opposing effects. Using a robust label-free quantitative proteomic methodology, we identified 12 of 13 plasma membrane intrinsic protein (PIP) aquaporin isoforms, 4 of the 10 tonoplast intrinsic protein isoforms, and a diversity of post-translational modifications including phosphorylation, methylation, deamidation, and acetylation. A total of 55 aquaporin peptides displayed significant changes after treatments and enabled the identification of specific and as yet unknown patterns of response to stimuli. The data show that the regulation of PIP and tonoplast intrinsic protein abundance was involved in response to a few treatments (i.e. NaCl, NO, and nitrate starvation), whereas changes in the phosphorylation status of PIP aquaporins were positively correlated to changes in root hydraulic conductivity in the whole set of treatments. The identification of in vivo deamidated forms of aquaporins and their stimulus-induced changes in abundance may reflect a new mechanism of aquaporin regulation. The overall work provides deep insights into the in vivo post-translational events triggered by environmental constraints and their possible role in regulating plant water status.


Assuntos
Aquaporinas/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/metabolismo , Processamento de Proteína Pós-Traducional , Água/metabolismo , Acetilação , Amidas/metabolismo , Sequência de Aminoácidos , Aquaporinas/genética , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Escuridão , Variação Genética , Peróxido de Hidrogênio/farmacologia , Manitol/farmacologia , Metilação , Anotação de Sequência Molecular , Dados de Sequência Molecular , Óxido Nítrico/farmacologia , Fosfatos/farmacologia , Fosforilação , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Cloreto de Sódio/farmacologia , Estresse Fisiológico , Sacarose/farmacologia
13.
BMC Health Serv Res ; 15: 500, 2015 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-26547908

RESUMO

BACKGROUND: School screening programs for adolescent idiopathic scoliosis (AIS) have been discontinued in Canada and elsewhere because they were not considered cost-effective. In communities lacking such programs, we expect a significant variety of healthcare pathways and timeframes for patient referrals to orthopaedics. The objectives of this study were: 1) to characterise the healthcare pathways of young children with suspected AIS in a population without school screening; and 2) to investigate the relationships between these healthcare pathways and the appropriateness of referrals to specialised orthopaedic clinics. METHODS: This study concerned all children, ages 10 to 18, referred for an initial visit for suspected AIS to any of the five out-patient paediatric orthopaedic clinics of south-western Quebec (Canada). For the 831 participants, referrals to orthopaedics were characterised as appropriate, late, or inappropriate, based on known risk factors for AIS progression and on treatment indications. Parents documented the circumstances of healthcare use prior to the orthopaedic consultation. Relevant predisposing, enabling, and need variables derived from Andersen's Behavioral Model of Health Services Use were also documented. Healthcare pathways were characterised by developing a taxonomy using multiple correspondence analysis prior to hierarchical classification. Associations between the healthcare pathways and appropriateness of referral were assessed using multinomial regression analyses. RESULTS: We constructed a taxonomy of five distinct healthcare pathways: 1) Lay/regular source of care interrelation, 2) Other professionals, 3) Lay/consultation discontinuity, 4) Other medical doctor, and 5) Regular source of care continuity. Laypersons played an important role in AIS suspicion (53% of cases), but did not prevent late referrals. Continuity of care, as opposed to numerous uncoordinated consultations, was an effective strategy to prevent late referrals (OR = 0.32 [0.17-0.59]), but was related to increased probability of inappropriate referrals. CONCLUSIONS: We identified two cardinal characteristics that distinguished the healthcare pathways and related significantly to appropriateness of referral status, namely the role of laypersons and the involvement of the regular source of care. This suggests directions for intervention such as advocating for access to a regular source of care, increasing awareness of the disease to medical practitioners' and improving their knowledge of AIS detection and referral criteria.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Ortopedia , Escoliose/diagnóstico , Adolescente , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Criança , Continuidade da Assistência ao Paciente , Estudos Transversais , Feminino , Humanos , Masculino , Pais , Pediatria , Quebeque , Encaminhamento e Consulta , Fatores de Risco , Escoliose/terapia
14.
Homeopathy ; 104(3): 170-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26143449

RESUMO

BACKGROUND: Utilization of sedative hypnotic drugs for sleeping disorders (SD) raises concerns, particularly among older people. This study compared utilization of conventional psychotropic drugs for SD among patients seeking care from general practitioners (GPs) who strictly prescribe conventional medications (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHODS: This was a French population-based cohort study of GPs and their patients consulting for SD, informed through the Pittsburgh sleep quality index (PSQI) questionnaire. Information on psychotropic drugs utilization was obtained from a standardized telephone interview at inclusion, one, three and 12 months. RESULTS: 346 patients consulting for SD were included. Patients in the GP-Ho group experienced more often severe SD (41.3%) than patients in the GP-CM group (24.3%). Adjusted multivariate analyses showed that patients who chose to be managed by GP-Ho were less likely to use psychotropic drugs over 12 months as opposed to the GP-CM group, with Odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.14 to 0.42. Patients in the GP-Mx group also used less psychotropic drugs but the result was not statistically significant (OR = 0.67; 95% CI: 0.39-1.16). Rates of clinical improvement of the SD did not differ between groups. CONCLUSIONS: Patients with SD who chose to consult GPs certified in homeopathy consumed less psychotropic drugs and had a similar evolution of their condition to patients treated with conventional medical management. This result may translate in a net advantage with reduction of adverse events related to psychotropic drugs.


Assuntos
Gerenciamento Clínico , Homeopatia/métodos , Atenção Primária à Saúde/métodos , Psicotrópicos/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Adulto , Idoso , Estudos de Coortes , Feminino , Homeopatia/normas , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/normas , Psicotrópicos/efeitos adversos , Inquéritos e Questionários , Adulto Jovem
15.
Proteomics ; 14(9): 1058-70, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24616185

RESUMO

An excess of NaCl in the soil is detrimental for plant growth. It interferes with mineral nutrition and water uptake and leads to accumulation of toxic ions in the plant. Understanding the response of roots to NaCl stress may facilitate the development of crops with increased tolerance to this and other stresses. Since controls achieved at the posttranslational level are of critical importance for regulating protein function, the present work used a robust label-free quantitative proteomic methodology to quantify phosphorylation events that affect root membrane proteins in Arabidopsis, in response to short-term (up to 2 h) NaCl treatments. This work identified 302 proteotypic phosphopeptides including 77 novel phosphorylated sites. NaCl treatment significantly altered the abundance of 74 phosphopeptides, giving novel insights into the regulation of major classes of membrane proteins, including ATPases, sodium transporters, and aquaporins. The data provide a unique access to phosphorylation reprogramming of ionic equilibrium in plant cells under NaCl stress. The use of predictive bioinformatic tools for kinase motifs suggested that root membrane proteins are substrates of cAMP-dependent protein kinase, cGMP-dependent protein kinase, and protein kinase C families, also called AGC kinases, arguing for an important role of lipid signaling in abiotic stress responses. It also pointed to cross-talks between protein kinase families during NaCl stress.


Assuntos
Proteínas de Arabidopsis/análise , Proteínas de Membrana/análise , Fosfoproteínas/análise , Raízes de Plantas/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Fosforilação , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Proteoma/análise , Proteoma/química , Proteoma/efeitos dos fármacos , Proteoma/metabolismo , Proteômica
16.
BMC Plant Biol ; 14: 102, 2014 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-24755305

RESUMO

BACKGROUND: Cecropin A is a natural antimicrobial peptide that exhibits rapid, potent and long-lasting lytic activity against a broad spectrum of pathogens, thus having great biotechnological potential. Here, we report a system for producing bioactive cecropin A in rice seeds. RESULTS: Transgenic rice plants expressing a codon-optimized synthetic cecropin A gene drived by an endosperm-specific promoter, either the glutelin B1 or glutelin B4 promoter, were generated. The signal peptide sequence from either the glutelin B1 or the glutelin B4 were N-terminally fused to the coding sequence of the cecropin A. We also studied whether the presence of the KDEL endoplasmic reticulum retention signal at the C-terminal has an effect on cecropin A subcellular localization and accumulation. The transgenic rice plants showed stable transgene integration and inheritance. We show that cecropin A accumulates in protein storage bodies in the rice endosperm, particularly in type II protein bodies, supporting that the glutelin N-terminal signal peptides play a crucial role in directing the cecropin A to this organelle, independently of being tagged with the KDEL endoplasmic reticulum retention signal. The production of cecropin A in transgenic rice seeds did not affect seed viability or seedling growth. Furthermore, transgenic cecropin A seeds exhibited resistance to infection by fungal and bacterial pathogens (Fusarium verticillioides and Dickeya dadantii, respectively) indicating that the in planta-produced cecropin A is biologically active. CONCLUSIONS: Rice seeds can sustain bioactive cecropin A production and accumulation in protein bodies. The system might benefit the production of this antimicrobial agent for subsequent applications in crop protection and food preservation.


Assuntos
Peptídeos Catiônicos Antimicrobianos/biossíntese , Endosperma/metabolismo , Oryza/metabolismo , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/química , Resistência à Doença/imunologia , Fusarium/fisiologia , Dosagem de Genes , Dados de Sequência Molecular , Mutagênese Insercional , Especificidade de Órgãos/genética , Organelas/metabolismo , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Plantas Geneticamente Modificadas , Reprodutibilidade dos Testes , Frações Subcelulares/metabolismo , Transgenes/genética
17.
Plant Cell ; 23(4): 1523-35, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21521698

RESUMO

In Arabidopsis thaliana, the PHOSPHATE TRANSPORTER1 (PHT1) family encodes the high-affinity phosphate transporters. They are transcriptionally induced by phosphate starvation and require PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR (PHF1) to exit the endoplasmic reticulum (ER), indicating intracellular traffic as an additional level of regulation of PHT1 activity. Our study revealed that PHF1 acts on PHT1, upstream of vesicle coat protein COPII formation, and that additional regulatory events occur during PHT1 trafficking and determine its ER exit and plasma membrane stability. Phosphoproteomic and mutagenesis analyses revealed modulation of PHT1;1 ER export by Ser-514 phosphorylation status. Confocal microscopy analysis of root tip cells showed that PHT1;1 is localized to the plasma membrane and is present in intracellular endocytic compartments. More precisely, PHT1;1 was localized to sorting endosomes associated with prevacuolar compartments. Kinetic analysis of PHT1;1 stability and targeting suggested a modulation of PHT1 internalization from the plasma membrane to the endosomes, followed by either subsequent recycling (in low Pi) or vacuolar degradation (in high Pi). For the latter condition, we identified a rapid mechanism that reduces the pool of PHT1 proteins present at the plasma membrane. This mechanism is regulated by the Pi concentration in the medium and appears to be independent of degradation mechanisms potentially regulated by the PHO2 ubiquitin conjugase. We propose a model for differential trafficking of PHT1 to the plasma membrane or vacuole as a function of phosphate concentration.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Transporte de Fosfato/metabolismo , Biossíntese de Proteínas , Sequência de Aminoácidos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/metabolismo , Compartimento Celular , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Endossomos/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Espaço Intracelular/metabolismo , Dados de Sequência Molecular , Especificidade de Órgãos , Proteínas de Transporte de Fosfato/química , Fosfatos/deficiência , Fosfatos/metabolismo , Fosforilação , Estabilidade Proteica , Transporte Proteico , Proteínas Recombinantes de Fusão/metabolismo
18.
Birth ; 41(1): 70-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24654639

RESUMO

OBJECTIVES: To critically appraise the literature on the relations between four intrapartum obstetric interventions-electronic fetal monitoring (EFM), epidural analgesia, labor induction, and labor acceleration; and two types of delivery-instrumental (forceps and vacuum) and cesarean section. METHODS: This review included meta-analyses published between January 2000 and April 2012 including at least one randomized clinical trial published after 1995 and presenting results on low-risk pregnancies between 37 and 42 weeks of gestation, searched in the databases Medline, Cochrane Library, and EMBASE with no language restriction. RESULTS: Of 306 documents identified, 8 fulfilled the inclusion criteria and presented results on women at low risk. EFM at admission (vs intermittent auscultation) was associated with cesarean delivery (odds ratio [OR] = 1.20, 95% confidence interval [CI] 1.00-1.44) and epidural analgesia (OR = 1.25, 95% CI 1.09-1.43). Epidural on request was associated with cesarean delivery (OR = 1.60, 95% CI 1.18-2.18), instrumental delivery (OR = 1.21, 95% CI 1.03-1.44), and oxytocin use (OR = 1.20, 95% CI 1.01-1.43) when compared with epidural on request plus nonpharmacological labor pain control methods such as one-to-one support, breathing techniques, and relaxation. Induction and acceleration of labor showed heterogeneous patterns of associations with cesarean delivery and instrumental delivery. CONCLUSIONS: Complex patterns of associations between obstetric interventions and modes of delivery were illustrated in an empirical model. Intermittent auscultation and nonpharmacological labor pain control interventions, such as one-to-one support during labor, have the potential for substantially reducing cesarean deliveries.


Assuntos
Analgesia Epidural/estatística & dados numéricos , Cesárea/estatística & dados numéricos , Extração Obstétrica/estatística & dados numéricos , Monitorização Fetal/estatística & dados numéricos , Trabalho de Parto Induzido/estatística & dados numéricos , Ocitócicos , Analgesia Obstétrica/estatística & dados numéricos , Feminino , Humanos , Razão de Chances , Gravidez
19.
Birth ; 41(2): 122-37, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24761801

RESUMO

OBJECTIVES: To assess the effects of nonpharmacologic approaches to pain relief during labor, according to their endogenous mechanism of action, on obstetric interventions, maternal, and neonatal outcomes. DATA SOURCE: Cochrane library, Medline, Embase, CINAHL and the MRCT databases were used to screen studies from January 1990 to December 2012. STUDY SELECTION: According to Cochrane criteria, we selected randomized controlled trials that compared nonpharmacologic approaches for pain relief during labor to usual care, using intention-to-treat method. RESULTS: Nonpharmacologic approaches, based on Gate Control (water immersion, massage, ambulation, positions) and Diffuse Noxious Inhibitory Control (acupressure, acupuncture, electrical stimulation, water injections), are associated with a reduction in epidural analgesia and a higher maternal satisfaction with childbirth. When compared with nonpharmacologic approaches based on Central Nervous System Control (education, attention deviation, support), usual care is associated with increased odds of epidural OR 1.13 (95% CI 1.05-1.23), cesarean delivery OR 1.60 (95% CI 1.18-2.18), instrumental delivery OR 1.21 (95% CI 1.03-1.44), use of oxytocin OR 1.20 (95% CI 1.01-1.43), labor duration (29.7 min, 95% CI 4.5-54.8), and a lesser satisfaction with childbirth. Tailored nonpharmacologic approaches, based on continuous support, were the most effective for reducing obstetric interventions. CONCLUSION: Nonpharmacologic approaches to relieve pain during labor, when used as a part of hospital pain relief strategies, provide significant benefits to women and their infants without causing additional harm.


Assuntos
Terapias Complementares/métodos , Parto Obstétrico/métodos , Manejo da Dor/métodos , Feminino , Humanos , Recém-Nascido , Análise de Intenção de Tratamento , Avaliação de Resultados da Assistência ao Paciente , Gravidez
20.
BMC Health Serv Res ; 14: 362, 2014 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-25168160

RESUMO

BACKGROUND: Even if a large proportion of physiotherapists work in the private sector worldwide, very little is known of the organizations within which they practice. Such knowledge is important to help understand contexts of practice and how they influence the quality of services and patient outcomes. The purpose of this study was to: 1) describe characteristics of organizations where physiotherapists practice in the private sector, and 2) explore the existence of a taxonomy of organizational models. METHODS: This was a cross-sectional quantitative survey of 236 randomly-selected physiotherapists. Participants completed a purpose-designed questionnaire online or by telephone, covering organizational vision, resources, structures and practices. Organizational characteristics were analyzed descriptively, while organizational models were identified by multiple correspondence analyses. RESULTS: Most organizations were for-profit (93.2%), located in urban areas (91.5%), and within buildings containing multiple businesses/organizations (76.7%). The majority included multiple providers (89.8%) from diverse professions, mainly physiotherapy assistants (68.7%), massage therapists (67.3%) and osteopaths (50.2%). Four organizational models were identified: 1) solo practice, 2) middle-scale multiprovider, 3) large-scale multiprovider and 4) mixed. CONCLUSIONS: The results of this study provide a detailed description of the organizations where physiotherapists practice, and highlight the importance of human resources in differentiating organizational models. Further research examining the influences of these organizational characteristics and models on outcomes such as physiotherapists' professional practices and patient outcomes are needed.


Assuntos
Especialidade de Fisioterapia/organização & administração , Setor Privado , Estudos Transversais , Feminino , Humanos , Masculino , Modelos Organizacionais , Cultura Organizacional , Quebeque , Inquéritos e Questionários
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