RESUMO
BACKGROUND: Longitudinal studies consistently report adverse long-term outcomes of childhood maltreatment. Little is known about the impact of childhood maltreatment on mental health among a marginalized population (New Zealand Maori); therefore, we cannot assume the effects of maltreatment are the same across the population. OBJECTIVE: Associations were examined between childhood sexual abuse (CSA), childhood physical punishment (CPP) and childhood neglect (CN) (<16 years) and mental health outcomes 18-40 years, by ethnicity (Maori/non-Maori). PARTICIPANTS AND SETTING: Data from the Christchurch Health and Development Study, a study of a birth cohort of 1265 children born in Christchurch in 1977. By age 40, 17.8 % (n = 191) reported New Zealand Maori ethnic identity; 82.2 % (n = 883) were non-Maori. METHODS: CSA, CPP (<16 years) were measured at 18, 21 years; CN was measured at 40 years. Major depression, anxiety disorder, suicidal ideation, alcohol abuse/dependence and cannabis abuse/dependence were measured at ages 21, 25, 30, 35 and 40 years. Childhood confounding variables controlled. Analyses were extended to include Maori ethnicity. RESULTS: After statistical adjustment, experience of severe childhood maltreatment increased odds of mental health problems 1.8-2.6×, compared to no maltreatment; the effects of maltreatment were similar for males and females. For Maori, some higher rates of mental health problems were seen among those maltreated, no statistically significant associations were detected after Bonferroni correction (among severe maltreatment vs. no maltreatment). Limitations should be considered when interpreting results. CONCLUSIONS: Exposure to childhood maltreatment has long-term effects into middle-age. Further research employing culturally-sensitive approaches may help clarify Maori childhood maltreatment outcomes.
Assuntos
Alcoolismo , Maus-Tratos Infantis , Transtorno Depressivo Maior , Feminino , Masculino , Pessoa de Meia-Idade , Humanos , Criança , Etnicidade , Estudos Longitudinais , Nova Zelândia/epidemiologia , Avaliação de Resultados em Cuidados de SaúdeRESUMO
The nucleolus and Cajal bodies (CBs) are sub-nuclear domains with well-known roles in RNA metabolism and RNA-protein assembly. However, they also participate in other important aspects of cell functioning. This study uncovers a previously unrecognised mechanism by which these bodies and their components regulate host defences against pathogen attack. We show that the CB protein coilin interacts with poly(ADP-ribose) polymerase 1 (PARP1), redistributes it to the nucleolus and modifies its function, and that these events are accompanied by substantial increases in endogenous concentrations of salicylic acid (SA), activation of SA-responsive gene expression and callose deposition leading to the restriction of tobacco rattle virus (TRV) systemic infection. Consistent with this, we also find that treatment with SA subverts the negative effect of the pharmacological PARP inhibitor 3-aminobenzamide (3AB) on plant recovery from TRV infection. Our results suggest that PARP1 could act as a key molecular actuator in the regulatory network which integrates coilin activities as a stress sensor for virus infection and SA-mediated antivirus defence.
Assuntos
Antivirais , Corpos Enovelados , Antivirais/metabolismo , Corpos Enovelados/genética , Ácido Salicílico/metabolismo , Poli(ADP-Ribose) Polimerases/genética , RNA/metabolismoRESUMO
BACKGROUND: CF is traditionally assessed in clinic. It is unclear if home monitoring of young people with CF is feasible or acceptable. The COVID-19 pandemic has made home monitoring more of a necessity. We report the results of CLIMB-CF, exploring home monitoring's feasibility and potential obstacles. METHODS: We designed a mobile app and enrolled participants with CF aged 2-17 years and their parents for six months. They were asked to complete a variety of measures either daily or twice a week. During the study, participants and their parents completed questionnaires exploring depression, anxiety and quality of life. At the end of the study parents and participants completed acceptability questionnaires. RESULTS: 148 participants were recruited, 4 withdrew prior to starting the study. 82 participants were female with median (IQR) age 7.9 (5.2-12 years). Median data completeness was 40.1% (13.6-69.9%) for the whole cohort; when assessed by age participants aged ≥ 12 years contributed significantly less (15.6% [9.8-30%]). Data completeness decreased over time. There was no significant difference between parental depression and anxiety scores at the start and the end of the study nor in CFQ-R respiratory domain scores for participants ≥ 14 years. The majority of participants did not feel the introduction of home monitoring impacted their daily lives. CONCLUSIONS: Most participants felt home monitoring did not negatively impact their lives and it did not increase depression, anxiety or decrease quality of life. However, uptake was variable, and not well sustained. The teenage years pose a particular challenge and further work is required.
Assuntos
Fibrose Cística/terapia , Aplicativos Móveis , Monitorização Fisiológica/métodos , Monitorização Fisiológica/psicologia , Qualidade de Vida , Adolescente , Ansiedade , COVID-19/epidemiologia , Criança , Pré-Escolar , Depressão , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: Healthcare worker (HCW) hand hygiene compliance is key to patient safety; however, compliance is suboptimal. Nevertheless hand hygiene compliance is not well studied in the long-term care setting. AIM: To apply a behaviour change framework, the Theoretical Domains Framework (TDF), to identify modifiable facilitators and barriers for HCW hand hygiene compliance in long-term care settings. METHODS: HCW hand hygiene compliance facilitators and barriers were examined using a questionnaire for HCWs from long-term care homes in Ontario, Canada. The questionnaire was informed by the TDF, which is based on a synthesis of constructs from a number of relevant psychological theories of behaviour change. FINDINGS: Barriers identified from the questionnaire aligned with the TDF domain environmental context and resources (time pressure, workload, and environmental controls). Facilitators identified from questionnaire results aligned with the TDF domains social/professional role and identity (it is what is expected of HCWs), and beliefs about consequences (risk of transmission of micro-organisms to self or others). CONCLUSION: There are several barriers to hand hygiene compliance that persist in long-term care. A behaviour change theory-informed framework such as the TDF can be helpful to identify those barriers. This study identified several key behavioural constructs aligned with the TDF that can be targeted when developing novel hand hygiene interventions.
Assuntos
Atitude do Pessoal de Saúde , Fidelidade a Diretrizes/estatística & dados numéricos , Higiene das Mãos/métodos , Higiene das Mãos/estatística & dados numéricos , Transmissão de Doença Infecciosa do Profissional para o Paciente/prevenção & controle , Assistência de Longa Duração , Utilização de Procedimentos e Técnicas , Comportamento , Feminino , Instalações de Saúde , Humanos , Masculino , Ontário , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Low-and-Middle-Income-Countries (LMICs) account for 75% of global suicides. While primary care populations in high-income countries (HIC) typically have higher prevalence of suicidal behavior relative to general populations, few studies have explored suicidal behavior among general medical outpatients in LMICs. This study addresses the research gap by characterizing potential risk factors for suicidal ideation in a large general medical outpatient setting in rural Kenya. METHODS: A cross-sectional study of adult general medical outpatients attending a rural sub-county hospital in Kaloleni, Kenya. Primary outcomes included major depressive disorder (MDD), posttraumatic stress disorder (PTSD) and suicidal behavior measured by the Mini International Neuropsychiatric Interview (MINI 5.0). We use binary logistic regression to model suicidality, mental disorders, intimate partner violence, and lifetime abuse. RESULTS: 394 outpatients completed the assessment. The prevalence of SI over the past month was 20%. 18% of those with suicidal ideation over the past month also attempted suicide in the past month. Participants who met criteria for MDD (suicidality item removed) were 19 times [CI: 4.56, 79.05] more likely to report suicidal ideation compared to those without MDD (adjusted odds ratio 12.15 [CI: 2.66, 55.49]). LIMITATIONS: This was a cross sectional study design with convenience sampling and hence vulnerable to selection and recall bias. CONCLUSION: The prevalence of SI and its strong association with actual suicide attempt in this population, make an urgent public health case for intervention. These data identify MDD as a highly significant correlate of SI.
Assuntos
Pacientes Ambulatoriais/estatística & dados numéricos , População Rural/estatística & dados numéricos , Ideação Suicida , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pacientes Ambulatoriais/psicologia , Prevalência , Fatores de Risco , Suicídio/psicologia , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto JovemRESUMO
The colonisation and establishment of the intestinal microbiota starts immediately at birth and is essential for the development of the intestine and the immune system. This microbial community gradually increases in number and diversity until the age of two or three years when it becomes a stable ecosystem resembling that of adults. This period constitutes a unique window of opportunity to modulate it through probiotic action, with a potential impact in later health. In the present work we have investigated how putative bifidobacterial probiotics modify the metabolic profiles and immune-modulatory properties of faecal microbiotas. An in vitro pH-controlled single-stage continuous-culture system (CCS) inoculated with infant faeces was employed to characterise the effects of two Bifidobacterium species on the intestinal microbiotas in three children, together with the effects of these modified microbiotas on cytokine production by HT-29 cells. Intestinal bacterial communities, production of short-chain fatty acids and lactate were determined by quantitative PCR and gas chromatography, respectively. Cytokines production by HT-29 cells was measured by ELISA. The combination of CCS with infant faeces and human intestinal cells provided a suitable model to evaluate the specific modulation of the intestinal microbiota and immune system by probiotics. In the CCS, infant faecal microbiotas were influenced by the addition of bifidobacteria, resulting in changes in their ability to induce the production of immune mediators by HT-29 cells. The different metabolic and immunological responses induced by the bifidobacterial species tested indicate the need to assess potential probiotics in model systems including complex intestinal microbiotas. Potential probiotic bifidobacteria can modulate the infant microbiota and its ability to induce the production of mediators of the immune response by intestinal cells.
Assuntos
Bifidobacterium/crescimento & desenvolvimento , Bifidobacterium/imunologia , Citocinas/metabolismo , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Microbioma Gastrointestinal/imunologia , Probióticos/metabolismo , Bifidobacterium/metabolismo , Cromatografia Gasosa , Ácidos Graxos Voláteis/metabolismo , Feminino , Células HT29 , Humanos , Lactente , Lactatos/metabolismo , Masculino , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The prevalence of obesity during pregnancy is rising. Elevated BMI is a significant risk factor for adverse maternal and fetal outcomes, including primary postpartum haemorrhage (PPH). Addressing the issues surrounding obesity in pregnancy presents many biological, social and psychological challenges. BMI is an easily measured and modifiable anthropometrical risk factor and should be recorded in all pregnancies. BMI should be proactively managed prior to and during pregnancy. All women should be educated as to the risks of an elevated BMI during pregnancy and those at risk should have access to specialist medical and surgical support if required. Our aim was to investigate the associations between elevated BMI and adverse maternal and fetal outcomes including PPH, and to explore the psychological challenges of having an elevated BMI during pregnancy.
Assuntos
Imagem Corporal/psicologia , Índice de Massa Corporal , Obesidade/epidemiologia , Obesidade/psicologia , Hemorragia Pós-Parto/epidemiologia , Volume Sanguíneo , Peso Corporal , Feminino , Hemoglobinas/metabolismo , Humanos , Hemorragia Pós-Parto/sangue , Gravidez , Fatores de RiscoRESUMO
Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER(+) breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Sobrevivência Celular/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas de Membrana/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteína 11 Semelhante a Bcl-2 , Sobrevivência Celular/genética , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/genética , Citometria de Fluxo , Humanos , Immunoblotting , Imuno-Histoquímica , Proteínas de Membrana/genética , Microscopia Confocal , Fosfatidilinositol 3-Quinases/genética , Proteína Quinase C/genética , Proteínas Proto-Oncogênicas/genética , Receptores de Lisoesfingolipídeo/genéticaRESUMO
BACKGROUND: Ageing can result in major changes in the composition and metabolic activities of bacterial populations in the large gut and an impaired immune system. AIM: To investigate the effects of synbiotic consumption on the colonic microbiota, immune function and health status in older people. METHODS: A randomised, double-blind placebo-controlled, 4-week crossover study was carried out, involving 43 older volunteers, using a synbiotic comprising the probiotic Bifidobacterium longum and an inulin-based prebiotic Synergy 1 (SudZucker, Mannheim, Germany). Faecal and blood samples were collected, and clinical status scored at the start, and at 2- and 4-week intervals, with a 4-week washout between each feeding period. Faecal bacteria were determined by fluorescent in situ hybridisation. Short-chain fatty acid concentrations, cytokine production, bowel habit and a range of clinical parameters were measured. RESULTS: The synbiotic increased bifidobacterial numbers by 1.4 log units (P < 0.0001) and also increased members of the phyla Actinobacteria and Firmicutes (P = 0.0004, P < 0.0001). Proteobacteria were reduced by 1.0 log units (P < 0.0001). Synbiotic feeding was associated with increased butyrate production (P = 0.0399). The pro-inflammatory response was modified by the synbiotic, with significantly reduced pro-inflammatory cytokine TNF-α in peripheral blood after 2 and 4 weeks of synbiotic consumption (P = 0.02, P = 0.0406). The synbiotic had no effect on bowel habit or any clinical parameters. CONCLUSION: Short-term synbiotic use can be effective in improving the composition and metabolic activities of colonic bacterial communities and immune parameters in older people. This study was registered at clinicaltrials.gov as NCT01226212.
Assuntos
Colo/microbiologia , Trato Gastrointestinal/microbiologia , Probióticos/administração & dosagem , Simbióticos , Idoso , Idoso de 80 Anos ou mais , Bifidobacterium , Estudos Cross-Over , Método Duplo-Cego , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Feminino , Humanos , Masculino , Microbiota , Prebióticos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Most plant viruses rely on vector organisms for their plant-to-plant spread. Although there are many different natural vectors, few plant virus-vector systems have been well studied. This review describes our current understanding of virus transmission by aphids, thrips, whiteflies, leafhoppers, planthoppers, treehoppers, mites, nematodes, and zoosporic endoparasites. Strategies for control of vectors by host resistance, chemicals, and integrated pest management are reviewed. Many gaps in the knowledge of the transmission mechanisms and a lack of available host resistance to vectors are evident. Advances in genome sequencing and molecular technologies will help to address these problems and will allow innovative control methods through interference with vector transmission. Improved knowledge of factors affecting pest and disease spread in different ecosystems for predictive modeling is also needed. Innovative control measures are urgently required because of the increased risks from vector-borne infections that arise from environmental change.
Assuntos
Quitridiomicetos/fisiologia , Hemípteros/fisiologia , Ácaros/fisiologia , Nematoides/fisiologia , Doenças das Plantas/prevenção & controle , Vírus de Plantas/fisiologia , Plasmodioforídeos/fisiologia , Animais , Quitridiomicetos/virologia , Vetores de Doenças , Hemípteros/virologia , Ácaros/virologia , Nematoides/virologia , Controle de Pragas , Doenças das Plantas/parasitologia , Doenças das Plantas/virologia , Plantas/microbiologia , Plantas/parasitologia , Plasmodioforídeos/virologiaRESUMO
ISSUES ADDRESSED: Community and school cooking and gardening programs have recently increased internationally. However, despite promising indications, there is limited evidence of their effectiveness. This paper presents the evaluation framework and methods negotiated and developed to meet the information needs of all stakeholders for the Stephanie Alexander Kitchen Garden (SAKG) program, a combined cooking and gardening program implemented in selectively funded primary schools across Australia. METHODS: The evaluation used multiple aligned theoretical frameworks and models, including a public health ecological approach, principles of effective health promotion and models of experiential learning. The evaluation is a non-randomised comparison of six schools receiving the program (intervention) and six comparison schools (all government-funded primary schools) in urban and rural areas of Victoria, Australia. A mixed-methods approach was used, relying on qualitative measures to understand changes in school cultures and the experiential impacts on children, families, teachers, parents and volunteers, and quantitative measures at baseline and 1 year follow up to provide supporting information regarding patterns of change. RESULTS: The evaluation study design addressed the limitations of many existing evaluation studies of cooking or garden programs. The multistrand approach to the mixed methodology maintained the rigour of the respective methods and provided an opportunity to explore complexity in the findings. Limited sensitivity of some of the quantitative measures was identified, as well as the potential for bias in the coding of the open-ended questions. CONCLUSION: The SAKG evaluation methodology will address the need for appropriate evaluation approaches for school-based kitchen garden programs. It demonstrates the feasibility of a meaningful, comprehensive evaluation of school-based programs and also demonstrates the central role qualitative methods can have in a mixed-method evaluation. So what? This paper contributes to debate about appropriate evaluation approaches to meet the information needs of all stakeholders and will support the sharing of measures and potential comparisons between program outcomes for comparable population groups and settings.
Assuntos
Comportamento Alimentar , Jardinagem , Promoção da Saúde , Instituições Acadêmicas , Grupos Focais , Projetos Piloto , Pesquisa Qualitativa , VitóriaRESUMO
SUMMARY: Barrett's oesophagus (BO) and gastro-oesophageal reflux disease (GERD) are precursors of oesophageal adenocarcinoma (OAC). There is an oesophageal biofilm, which changes in disease, but its role in aetiopathogenesis remains unclear. AIM: To define the oesophageal microbiota of patients with GERD, BO and OAC compared with controls and to investigate mucosal responses related to the microbiota. METHODS: Cultural analysis identified the dominant bacterial species from a subset of each disease group. Based on this, molecular techniques were used to define the cohort. Host responses were analysed in tissues and co-culture experiments. RESULTS: A total of 111 species belonging to 26 genera were isolated. There was a significant decrease in bacterial counts in the GERD and BO groups for all genera except Campylobacter, which colonised GERD and Barrett's patients in increasing numbers. Campylobacter concisus was the dominant species. This relationship was not seen in the cancer group. Significant increases in IL-18 were seen in GERD and BO colonised by Campylobacter. CONCLUSIONS: This study defines differences in the oesophageal biofilm in disease states, revealing the emergence of C. concisus as the dominant new colonist in the refluxed oesophagus. We also associate the presence of these bacteria with increased expression of cytokines related to carcinogenesis.
Assuntos
Adenocarcinoma/microbiologia , Esôfago de Barrett/microbiologia , Biofilmes/crescimento & desenvolvimento , Neoplasias Esofágicas/microbiologia , Refluxo Gastroesofágico/microbiologia , Metagenoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Fisiológicos Bacterianos , Estudos de Casos e Controles , Técnicas de Cocultura , Estudos de Coortes , Contagem de Colônia Microbiana , Citocinas/genética , Esôfago/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemAssuntos
Substituição de Aminoácidos , Complexos Multiproteicos/metabolismo , Nicotiana/metabolismo , Fases de Leitura Aberta , Fator 1 de Elongação de Peptídeos/metabolismo , Proteínas de Plantas/metabolismo , RNA Viral/metabolismo , Vírus do Mosaico do Tabaco/metabolismo , Proteínas Virais/metabolismo , Complexos Multiproteicos/genética , Fator 1 de Elongação de Peptídeos/genética , Proteínas de Plantas/genética , Ligação Proteica/genética , RNA Viral/genética , Nicotiana/genética , Nicotiana/virologia , Vírus do Mosaico do Tabaco/genética , Proteínas Virais/genéticaRESUMO
AIMS: To investigate the effects of human gut micro-organisms on cytokine production by human intestinal cell lines. METHODS AND RESULTS: Quantitative real-time PCR assays were developed to measure the production of pro-inflammatory (IL-1α, IL-6, IL-18 and TNFα) and anti-inflammatory (TGF-ß1, TGF-ß2, TGF-ß3, IL-4 and IL-10) cytokines in HT-29 and Caco-2 cell lines. They were co-cultured with a range of mucosal bacteria isolated from ulcerative colitis patients, together with lactobacilli and bifidobacteria obtained from healthy people. HT-29 cells were also co-cultured with Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli and Salmonella typhimurium. The majority of commensal bacteria tested suppressed the expression of anti-inflammatory cytokine mRNA, increased IL-18, reduced IL-1α, and with the exception of nonpathogenic E. coli, reduced TNF-α. All overtly pathogenic species increased both pro-inflammatory and anti-inflammatory cytokine mRNA. CONCLUSION: Commensal and pathogenic species induced fundamentally different cytokine responses in human intestinal epithelial cell lines. SIGNIFICANCE AND IMPACT OF THE STUDY: Interactions between commensal bacteria tested in this study and the innate immune system were shown to be anti-inflammatory in nature, in contrast to the pathogenic organisms investigated. These data contribute towards our understanding of how potential probiotic species can be used to suppress the pro-inflammatory response in inflammatory bowel disease.
Assuntos
Fenômenos Fisiológicos Bacterianos , Citocinas/biossíntese , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Bifidobacterium/fisiologia , Células CACO-2 , Campylobacter jejuni/fisiologia , Técnicas de Cocultura , Colite Ulcerativa/microbiologia , Citocinas/genética , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Escherichia coli/fisiologia , Células HT29 , Humanos , Interleucinas/biossíntese , Interleucinas/genética , Lactobacillus/fisiologia , Probióticos , Salmonella typhimurium/fisiologia , Fator de Crescimento Transformador beta/biossíntese , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
The complete nucleotide sequence of a UK strain of the sadwavirus Black raspberry necrosis virus (BRNV) was obtained by amplification and sequencing of virus RNA from infected plants grown in a raspberry plantation in Aylth, Scotland. The RNA1 was 7,572 nucleotides (nt) in size and RNA2 was 6,350 nt in size, each excluding the 3' poly-A tail. The RNA1- and RNA2-encoded polyproteins are predicted to be processed into (RNA1) a protease cofactor, an RNA helicase, the VpG, a 3C-like protease, an RNA-dependent RNA polymerase and an AlkB protein, and (RNA2) a movement protein and two capsid proteins.
Assuntos
Vírus de Plantas/classificação , Vírus de Plantas/genética , Rosaceae/virologia , Genoma Viral , EscóciaRESUMO
BACKGROUND: Crohn's disease is an inflammatory illness in which the immune response against gut microorganisms is believed to drive an abnormal immune response. Consequently, modification of mucosal bacterial communities, and the immune effects they elicit, might be used to modify the disease state. AIM: To investigate the effects of synbiotic consumption on disease processes in patients with Crohn's disease. METHODS: A randomized, double-blind placebo-controlled trial was conducted involving 35 patients with active Crohn's disease, using a synbiotic comprising Bifidobacterium longum and Synergy 1. Clinical status was scored and rectal biopsies were collected at the start, and at 3- and 6-month intervals. Transcription levels of immune markers and mucosal bacterial 16S rRNA gene copy numbers were quantified using real-time PCR. RESULTS: Significant improvements in clinical outcomes occurred with synbiotic consumption, with reductions in both Crohn's disease activity indices (P = 0.020) and histological scores (P = 0.018). The synbiotic had little effect on mucosal IL-18, INF-gamma and IL-1beta; however, significant reductions occurred in TNF-alpha expression in synbiotic patients at 3 months (P = 0.041), although not at 6 months. Mucosal bifidobacteria proliferated in synbiotic patients. CONCLUSION: Synbiotic consumption was effective in improving clinical symptoms in patients with active Crohn's disease.
Assuntos
Bifidobacterium/metabolismo , Doença de Crohn/tratamento farmacológico , Mucosa Intestinal/microbiologia , Lactobacillus acidophilus/metabolismo , Oligossacarídeos/uso terapêutico , Probióticos/uso terapêutico , Adulto , Idoso , Contagem de Colônia Microbiana , Doença de Crohn/imunologia , Método Duplo-Cego , Feminino , Humanos , Mucosa Intestinal/imunologia , Masculino , Pessoa de Meia-Idade , Prebióticos , Probióticos/farmacologia , Resultado do TratamentoRESUMO
Intestinal microflora play a critical role in the initiation and perpetuation of chronic inflammatory bowel diseases. In genetically susceptible hosts, bacterial colonization results in rapid-onset chronic intestinal inflammation. Nevertheless, the intestinal and systemic immune response to faecal bacteria and antigen exposure into a sterile intestinal lumen of a post-weaned animal with a mature immune system are not understood clearly. This study examined the effects of faecal bacteria and antigen exposure on the intestinal mucosal and systemic immune system in healthy axenic mice. Axenic wild-type mice were inoculated orally with a crude faecal slurry solution derived from conventionally raised mice and were analysed prior to and then at days 3, 7, 14 and 28 post-treatment. Ingestion of faecal slurry resulted in a transient, early onset of proinflammatory interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-17 response that was maximal at day 3. In contrast, the transient release of the anti-inflammatory cytokines IL-10 and IL-4 occurred later and was maximal at day 7. Both responses subsided by day 14. This early cytokine imbalance was associated with a brief rise in colonic and caecal histopathological injury score at day 7. The bacterial antigen-specific systemic response was found to follow the intestinal immune response with a maximal release of both pro- and anti-inflammatory cytokines at day 7. Thus, first exposure of healthy axenic wild-type mice to normal faecal flora and antigens results in an early proinflammatory cytokine response and transient colonic inflammation that then resolves in conjunction with a subsequent anti-inflammatory cytokine profile.
Assuntos
Antígenos de Bactérias/administração & dosagem , Colite/etiologia , Fezes/microbiologia , Vida Livre de Germes/imunologia , Ileíte/etiologia , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Mucosa Intestinal/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Administração Oral , Animais , Antígenos de Bactérias/imunologia , Bacteroides/imunologia , Ceco/metabolismo , Ceco/microbiologia , Ceco/patologia , Colite/microbiologia , Colite/patologia , Colo/metabolismo , Colo/microbiologia , Colo/patologia , Enterococcus/imunologia , Ileíte/microbiologia , Ileíte/patologia , Íleo/metabolismo , Íleo/microbiologia , Íleo/patologia , Mucosa Intestinal/química , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Limosilactobacillus reuteri/imunologia , Camundongos , Permeabilidade , Organismos Livres de Patógenos Específicos , Linfócitos T/imunologia , Tiflite/etiologia , Tiflite/microbiologia , Tiflite/patologiaRESUMO
OBJECTIVE: Although the evidence base for the use of antipsychotics in older people with schizophrenia is generally of low quality, it tends to support the use of atypical antipsychotics. Only limited information regarding longer term adherence to these apparently more effective drugs is available. The aim of this study was to determine predictors of adherence to risperidone or olanzapine in patients over 60. METHODS: Patients receiving care from old age psychiatrists for their schizophrenia were randomised to treatment with olanzapine or risperidone and were followed for up to 3(1/2) years. Kaplan-Meier curves were generated to assess the univariate effect of randomisation drug on long-term adherence and Cox regression adjusted for baseline variables which may have affected adherence. RESULTS: In total, 60.6% of the 66 patients in the study were still taking their randomised drug by the end of the interval in which they remained under observation (64.7% olanzapine and 56.3% risperidone). This difference was non-significant. No baseline variable was associated with an increased risk of non-adherence, though the delivery form of pre-randomisation drug (oral or depot) was weakly (p = 0.054) associated with patients originally on depot being less likely to be adherent to an atypical drug. CONCLUSIONS: Overall adherence with atypical medication was good with almost two-thirds of the patients remaining on their randomisation drug for the interval in which they were under observation. Patients taken off depot were less likely to be adherent but there was no significant difference in adherence between olanzapine and risperidone. Scrutiny of the survival curves suggested that non-adherence is an early event in treatment and patients adherent at 6 months were likely to remain adherent over a longer time period.
Assuntos
Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Adesão à Medicação , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Olanzapina , Modelos de Riscos ProporcionaisRESUMO
Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.
Assuntos
Inflamação/fisiopatologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Artrite Reumatoide/dietoterapia , Artrite Reumatoide/fisiopatologia , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/fisiopatologia , Doença Celíaca/dietoterapia , Doença Celíaca/fisiopatologia , Humanos , Inflamação/dietoterapia , Doenças Inflamatórias Intestinais/dietoterapia , Doenças Inflamatórias Intestinais/fisiopatologia , Obesidade/dietoterapia , Obesidade/fisiopatologia , Hipersensibilidade Respiratória/dietoterapia , Hipersensibilidade Respiratória/fisiopatologia , Dermatopatias/dietoterapia , Dermatopatias/fisiopatologiaRESUMO
Crohn's disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is no clear evidence for a single transmissible agent being involved in IBD aetiology. Although marked alterations occur in faecal and mucosal bacterial communities in IBD, it is unclear whether they are responsible for causing disease, or are due to changes in the gut environment that result from inflammatory reactions and extensive tissue destruction. Despite the involvement of microorganisms in inflammatory processes, antibiotic therapy has generally been unsuccessful in IBD. However, recent studies involving the use of probiotics, prebiotics and synbiotics suggest that there is potential for controlling these diseases through manipulation of the composition of the gut microbiota, and direct interactions with the gut immune system.