Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 86
Filtrar
1.
Autism ; 25(4): 1090-1099, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33406885

RESUMO

LAY ABSTRACT: To date, studies using cross-sectional methodologies make up a majority of the literature surrounding children with autism spectrum disorders and participation in physical activity and screen time. Longitudinal studies are needed to examine how physical activity and screen time behaviors co-develop for children with and without an autism spectrum disorder. To address this research gap, this study compared how physical activity and screen time levels changed over time (from 9 to 18 years of age) between youth with autism spectrum disorder and youth with neurotypical development. Data on the levels of moderate-to-vigorous physical activity, light physical activity, television-, and video game-based screen time, collected as a part of the "Growing up in Ireland" study, were compared between youth with autism spectrum disorder and a propensity-matched sample of youth with neurotypical development (n = 88 per group; 176 in total). Robust regression analyses indicated that children with autism spectrum disorder became less active over time compared to children with neurotypical development and that video game screen time also differed significantly between the groups when children were 9 years old. These findings elucidate important disparities present between these groups of children during pivotal developmental times.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Adolescente , Criança , Estudos Transversais , Exercício Físico , Humanos , Irlanda/epidemiologia , Tempo de Tela , Fatores de Tempo
2.
Acute Med ; 19(4): 244-249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33215179

RESUMO

These case reports look at two patients with anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis presenting to the same acute medical unit within a month of each other. The following covers the characteristic signs, symptoms and timeline associated with this condition and discusses whether we should be sending CSF for anti-NMDAr antibody testing more readily.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Humanos
3.
Earth Space Sci ; 7(7): e2019EA000942, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32999896

RESUMO

A new model was recently introduced to correct for higher-order ionospheric residual biases in radio occultation (RO) data. The model depends on the α 1 and α 2 dual-frequency bending angle difference squared, and a factor κ, which varies with time, season, solar activity, and height, needing only the F10.7 solar radio flux index as additional background information. To date, this kappa-correction was analyzed in simulation studies. In this study, we test it on real observed Metop-A RO data. The goal is to improve the accuracy of monthly mean RO climate records, potentially raising the accuracy of RO data toward higher stratospheric altitudes. We performed a thorough analysis of the kappa-correction, evaluating its ionospheric sensitivity during the solar cycle for monthly RO climatologies and comparing the kappa-corrected RO stratospheric climatologies to three other data sets from reanalysis and passive infrared sounding. We find a clear dependence of the kappa-correction on solar activity, geographic location, and altitude; hence, it reduces systematic errors that vary with the solar cycle. From low to high solar activity conditions, the correction can increase from values of about 0.2 K to more than 2.0 K at altitudes between 40 to 45 km. The correction shifts RO climatologies toward warmer temperatures. With respect to other data sets, however, we found it difficult to draw firm conclusions, because the biases in the other data sets appear to be at similar magnitude as the size of the kappa-correction. Further validation with more accurate data will be useful.

4.
Surgeon ; 18(5): e1-e6, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31718929

RESUMO

BACKGROUND: Changes to working practices and increasing service demand have contributed to low morale amongst UK surgical trainees, with pressures particularly acute 'out of hours' (OOH). Surgeons may be expected to be 'on call' for multiple hospitals, or to provide remote consultations, yet healthcare systems may undermine their professional safety and patient care. This cross-sectional study sought to define the perceptions of UK-based Royal College of Surgeons of Edinburgh (RCSEd) affiliated trainees of OOH surgical care and training. METHODS: The RCSEd Trainees' Committee conducted a design-thinking exercise to produce an online questionnaire. Non-consultant grade RCSEd Members and Fellows were invited to participate. Quantitative data was analysed using descriptive statistics, and qualitative data was coded to identify emergent themes. RESULTS: One hundred and fifty-five surgeons participated. Of those surgeons working in multiple hospitals OOH (n = 16), many did not receive access cards (12[75%]) or site-specific induction (13[81%]), and 8(50%) were not confident in using local electronic investigation and records systems. Only 14/114 (12%) of the surgeons providing remote opinion had access to a consultation record system, and most perceived dissatisfaction with the system. Emergent themes from qualitative data revealed that trainee surgeons desire specific training in OOH working, concerns that OOH work experience is diminishing, and that hospital infrastructure such as IT and communications, rest facilities and catering were inadequate in facilitating safe care. CONCLUSIONS: The participants perceived that the systems supporting delivery of safe surgical care OOH were inadequate. Hospital leaders should ensure that systems minimise risk to staff and patients.


Assuntos
Plantão Médico/organização & administração , Educação de Pós-Graduação em Medicina/organização & administração , Cirurgia Geral/educação , Admissão e Escalonamento de Pessoal/organização & administração , Medicina Estatal , Competência Clínica , Estudos Transversais , Humanos , Inquéritos e Questionários , Reino Unido , Carga de Trabalho
5.
Ir J Psychol Med ; 36(3): 187-193, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30854993

RESUMO

OBJECTIVES: The transition from adolescent to adult mental health services (AMHS) is associated with disengagement, poor continuity of care and patient dissatisfaction. The aim of this retrospective and descriptive study was to describe the 'care pathways' in an independent mental health service when adolescents reach age 18 and to investigate the level of engagement of those who transitioned to independent AMHS. METHODS: This is a retrospective, naturalistic and descriptive study in design. All patients discharged from the St Patrick's Adolescent Mental Health Service aged 17 years and 6 months and older, during a 3-year period between January 2014 and December 2016, were included. Electronic records were used to collect socio-demographic and clinical details and to determine engagement rates in adolescents who transferred to independent adult services. RESULTS: A total of 180 patients aged over 17 years and 6 months were discharged from the adolescent service. Of these, 45.6% were discharged to their GP, 28.9% to public mental health services and 25.6% to independent mental health services. The majority who transitioned to independent AMHS went to a Young Adult Service, which had high engagement rates at 3 and 12 months post-transition. CONCLUSIONS: In this independent mental health service, less than half of adolescents who reach the transition age are referred onto AMHS. Engagement rates were found to be high among those referred on to a specialised young adult service.


Assuntos
Serviços de Saúde do Adolescente/estatística & dados numéricos , Serviços de Saúde Mental/estatística & dados numéricos , Transição para Assistência do Adulto , Adolescente , Adulto , Feminino , Humanos , Irlanda , Masculino , Transtornos Mentais/psicologia , Transtornos Mentais/terapia , Alta do Paciente , Estudos Retrospectivos , Adulto Jovem
7.
Biol Lett ; 13(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29212749

RESUMO

Hummingbirds feed from hundreds of flowers every day. The properties of these flowers provide these birds with a wealth of information about colour, space and time to guide how they forage. To understand how hummingbirds might use this information, researchers have adapted established laboratory paradigms for use in the field. In recent years, however, experimental inspiration has come less from other birds, and more from looking at other nectar-feeders, particularly honeybees and bumblebees, which have been models for foraging behaviour and cognition for over a century. In a world in which the cognitive abilities of bees regularly make the news, research on the influence of ecology and sensory systems on bee behaviour is leading to novel insights in hummingbird cognition. As methods designed to study insects in the laboratory are being applied to hummingbirds in the field, converging methods can help us identify and understand convergence in cognition, behaviour and ecology.


Assuntos
Aves/fisiologia , Cognição , Animais , Abelhas/fisiologia , Polinização
8.
BMC Psychiatry ; 17(1): 277, 2017 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-28754160

RESUMO

BACKGROUND: Low- and middle-income countries (LMICs) face a lack of epidemiological data. The development of high-quality surveys is a key research priority in countries such as Brazil. Our aim is to discuss the difficulties in conducting a longitudinal epidemiological survey in a pilot study of a school-based sample in São Paulo. METHODS: Data came from a cohort of school-attending adolescents in two neighborhoods with different levels of urbanicity in São Paulo. Students born in 2002 and in the 7th grade during 2014 were recruited from nine public schools. Adolescents and caregivers were interviewed separately at baseline and at one year follow-up, using several instruments, including the Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Version (K-SADS-PL). RESULTS: Achieving unbiased sampling, keeping an updated register of participants' contact information, using a full clinical interview without an algorithm for its scoring, and maintaining a highly-trained research team were among the difficulties faced. CONCLUSION: Working closely with community leaders, organizing group efforts to perform interviews, using a short, easy to understand instrument and providing some reward for participants were identified as alternatives to dealing with these difficulties, useful not only in Brazil, but also in other LMICs.


Assuntos
Coleta de Dados/métodos , Transtornos do Humor/epidemiologia , Projetos de Pesquisa , Esquizofrenia/epidemiologia , Estudantes/estatística & dados numéricos , Adolescente , Viés , Brasil/epidemiologia , Criança , Feminino , Humanos , Renda , Estudos Longitudinais , Masculino , Projetos Piloto , Sistema de Registros , Reprodutibilidade dos Testes , Instituições Acadêmicas/estatística & dados numéricos , Estudantes/psicologia
9.
J Neurol ; 262(11): 2596-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26514835
10.
J Neuroendocrinol ; 27(2): 158-65, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25514990

RESUMO

During nest building in zebra finches (Taeniopygia guttata), several regions in the social behaviour network and the dopaminergic reward system, which are two neural circuits involved in social behaviour, appear to be active in male and female nest-building finches. Because the nonapeptides, mesotocin and vasotocin and the neurotransmitter, dopamine, play important roles in avian social behaviour, we tested the hypothesis that mesotocinergic-vasotocinergic and dopaminergic neuronal populations in the social behaviour network and dopaminergic reward system, respectively, are active during nest building. We combined immunohistochemistry for Fos (an indirect marker of neuronal activity) and vasotocin, mesotocin or tyrosine hydroxylase on brain tissue from nest-building and non-nest-building male and female zebra finches and compared Fos immunoreactivity in these neuronal populations with the variation in nest-building behaviour. Fos immunoreactivity in all three types of neuronal populations increased with some aspect of nest building: (i) higher immunoreactivity in a mesotocinergic neuronal population of nest-building finches compared to controls; (ii) increased immunoreactivity in the vasotocinergic neuronal populations in relation to the amount of material picked up by nest-building males and the length of time that a male spent in the nest with his mate; and (iii) increased immunoreactivity in a dopaminergic neuronal population in relation to the length of time that a male nest-building finch spent in the nest with his mate. Taken together, these findings provide evidence for a role of the mesotocinergic-vasotocinergic and dopaminergic systems in avian nest building.


Assuntos
Dopamina/fisiologia , Tentilhões/fisiologia , Comportamento de Nidação/fisiologia , Ocitocina/análogos & derivados , Vasotocina/fisiologia , Animais , Feminino , Masculino , Ocitocina/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo
11.
Int J Tuberc Lung Dis ; 18(12): 1390-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25517802

RESUMO

The tuberculosis (TB) control strategy in the Republic of Karakalpakstan, Uzbekistan, is being changed to decentralised out-patient care for most TB patients by the Government of Uzbekistan, in collaboration with the international medical humanitarian organisation Médecins Sans Frontières. Ambulatory treatment of both drug-susceptible and drug-resistant TB from the first day of treatment has been recommended since 2011. Out-patient treatment of TB from the beginning of treatment was previously prohibited. However, the current Uzbek health financing system, which evolved from the Soviet Semashko model, offers incentives that work against the adoption of ambulatory TB treatment. Based on the 'Comprehensive TB Care for All' programme implemented in Karakalpakstan, we describe how existing policies for the allocation of health funds complicate the scale-up of ambulatory-based management of TB.


Assuntos
Assistência Ambulatorial/economia , Atenção à Saúde/economia , Financiamento Governamental/economia , Regulamentação Governamental , Custos de Cuidados de Saúde , Política de Saúde/economia , Tuberculose/economia , Tuberculose/terapia , Assistência Ambulatorial/legislação & jurisprudência , Assistência Ambulatorial/organização & administração , Orçamentos/legislação & jurisprudência , Continuidade da Assistência ao Paciente/economia , Continuidade da Assistência ao Paciente/legislação & jurisprudência , Atenção à Saúde/legislação & jurisprudência , Atenção à Saúde/organização & administração , Financiamento Governamental/legislação & jurisprudência , Financiamento Governamental/organização & administração , Custos de Cuidados de Saúde/legislação & jurisprudência , Reforma dos Serviços de Saúde/economia , Reforma dos Serviços de Saúde/legislação & jurisprudência , Política de Saúde/legislação & jurisprudência , Humanos , Modelos Organizacionais , Formulação de Políticas , Tuberculose/diagnóstico , Uzbequistão
12.
Urology ; 83(5): 1003-5, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24529588

RESUMO

OBJECTIVE: To demonstrate a cost benefit while using disposable laser fibers as compared with reusable laser fibers. Flexible ureteroscopy (FURS) is a central component of endourology. It is vital that for service provision and training purposes, costs are kept down while delivering this service. Laser fibers are known to damage scopes causing high repair and/or replacement costs. MATERIALS AND METHODS: Data for consecutive FURS procedures during 2 periods in a single center were compared. First, with the use of reusable fibers and second, with single-use fibers. Cost of laser fibers and repairs was recorded. The study excludes the cost of the initial purchase of the ureterorenoscopes or the holmium laser equipment and costs associated with staffing and hospital stay. RESULTS: The total number of FURS carried out in period 1 and period 2 was 260 and 265, respectively. A total of 13 reusable (185 procedures) and 168 disposable laser fibers were used in these 2 periods, respectively. There was a reduction in laser damaged ureteroscopes from 9 to 3 in the second period. This resulted in a £ 16,800 reduction in repair cost. This more than offsets the increased costs of single-use fibers. CONCLUSION: On the basis of our data, it is more cost-effective to use a disposable laser fiber, as it prevents scope damage, which can happen because of microfractures with repeated laser use. Moreover, this will also save time and/or resource required with sterilization.


Assuntos
Equipamentos Descartáveis/economia , Ureteroscópios/economia , Ureteroscopia/economia , Custos e Análise de Custo , Desenho de Equipamento , Humanos , Rim , Lasers , Fatores de Tempo
13.
Occup Ther Health Care ; 27(4): 355-71, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24102591

RESUMO

To investigate the use and potential for patient acceptance of the DrivingHealth(®) Inventory (DHI) in clinical practice, we administered the DHI to 360 community dwelling volunteers over age 50 at a Southeastern US rehabilitation hospital. Volunteers also completed surveys to document their health, driving habits, and impressions of the DHI. Volunteers reported strong agreement with statements that indicated that they believe the DHI measures abilities important for safe driving and that they would be willing to listen to advice about driving and safe mobility from medical professionals; however, responses to some items were more positive among drivers whose DHI results indicated no apparent loss of function that could impair driving. These results support the use of the DHI in clinical practice as a tool to raise awareness of factors that correlate to driving; however, further research will be necessary to investigate how the DHI may benefit diverse clinical populations. Experiences with using DHI as part of clinical practice are also discussed.


Assuntos
Atitude , Condução de Veículo , Nível de Saúde , Programas de Rastreamento , Segurança , Idoso , Idoso de 80 Anos ou mais , Conscientização , Coleta de Dados , Feminino , Humanos , Masculino , Memória , Saúde Mental , Pessoa de Meia-Idade , Aptidão Física , Centros de Reabilitação , Sudeste dos Estados Unidos , Inquéritos e Questionários , Acuidade Visual
14.
Childs Nerv Syst ; 29(11): 2095-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23681311

RESUMO

OBJECTIVE: This study aims to assess the efficacy and safety of vagal nerve stimulation (VNS) in children less than 12 years old operated on at the University Hospital Wales. METHOD: Retrospective review of patients undergoing VNS insertion, over a 3-year period, was undertaken. All children had a minimum follow-up period of 2 years. Sixteen patients were identified via the paediatric epilepsy surgery database. A case note review and telephone evaluation was conducted. Seizure frequency using the McHugh classification was the primary outcome measure, with anti-epileptic drug (AED) use as a secondary outcome measure. RESULTS: There were 10 males and 6 females. The mean time with epilepsy prior to surgery was 5.7 years and the mean age at the time of surgery was 7.6 years. Overall, nine (56 %) children experienced a reduction in their seizure frequency of 50 % or more. Of these, four (25 %) had a reduction of more than 80 %. Seven children (44 %) had no reduction in their seizure frequency, although two of these patients reported benefit regarding seizure control and post-ictal recovery. The VNS system was removed in two patients due to infection and no benefit, respectively. Half of the cohort (50 %) reduced the number of anti-epileptic drugs post-surgery, and there was an overall mean reduction of AED of 0.5. CONCLUSION: This study suggests that VNS is a safe and effective adjuvant therapy in children under 12 years old, with over half reporting significant benefit. Further studies are needed to enable preoperative selection of patients in order to maximise the potential benefit.


Assuntos
Epilepsia/terapia , Estimulação do Nervo Vago/métodos , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Remoção de Dispositivo , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Convulsões/cirurgia , Resultado do Tratamento , Estimulação do Nervo Vago/efeitos adversos , Estimulação do Nervo Vago/instrumentação
15.
Ir J Psychol Med ; 30(2): 103-111, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30199971

RESUMO

OBJECTIVES: To conduct a study looking at the prevalence and nature of Internet and mobile phone use in young people, focusing particularly on cyberbullying and its potential effects on young people's mental health. METHOD: Three secondary schools in an area of North Dublin were randomly selected, which included one all boys school, one all girls school and one co-educational school. Written information about the study was given to each school principal and to parents/carers of all first and second year students. First and second year students in each school from whom consent had been received were asked to complete two questionnaires, which included a questionnaire on cyberbullying and a self-report version of the Strengths and Difficulties Questionnaire (SDQ). A total of 130 students completed the study. RESULTS: A total of 24 (18.46%) pupils were cyberbullied. Of these, 13 (65% of those cyberbullied) pupils who were cyberbullied said that it had a negative effect on their mood, and 9 (45% of those cyberbullied) said that cyberbullying had a negative effect on their overall mental health. A statistically significant higher proportion of pupils who were cyberbullied scored in the Abnormal/Borderline range of the SDQ, compared with those who were not cyberbullied. CONCLUSION: This is the first study in Ireland, which looks at the potential mental health difficulties associated with cyberbullying. It is hoped that the information from this study will help to increase awareness of the effects of cyberbullying and help look at ways of managing cyberbullying.

16.
Br J Cancer ; 106(12): 2016-24, 2012 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-22669161

RESUMO

BACKGROUND: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. METHODS: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. RESULTS: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10-2.04 and HR 2.16, 95%CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. CONCLUSION: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Neoplasias Ovarianas/genética , Polimorfismo Genético , Proteínas Repressoras/genética , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Mutação , Proibitinas , Risco
17.
J Dairy Sci ; 95(7): 3954-60, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22720949

RESUMO

The effect of proximity to a dominant cow on a low-ranking cow's willingness to feed was assessed using choice tests. The main aim of the experiment was to determine the feeding space allowance at which the majority of subordinate cows would choose to feed on high-palatability food (HPF) next to a dominant cow rather than feeding alone on low-palatability food (LPF). Thirty Holstein-Friesian cows were used in the study. Half of the cows were trained to make an association between a black bin and HPF and a white bin and LPF, and the other half were trained with the opposite combination. Observations of pair-wise aggressive interactions were observed during feeding to determine the relative social status of each cow. From this, dominant and subordinate cows were allocated to experimental pairs. When cows had achieved an HPF preference with an 80% success rate in training, they were presented with choices using a Y-maze test apparatus, in which cows were offered choices between feeding on HPF with a dominant cow and feeding on LPF alone. Four different space allowances were tested at the HPF feeder: 0.3, 0.45, 0.6, and 0.75 m. At the 2 smaller space allowances, cows preferred to feed alone (choices between feeding alone or not for 0.3- and 0.45-m tests were significantly different). For the 2 larger space allowances, cows had no significant preferences (number of choices for feeding alone or with a dominant). Given that low-status cows are willing to sacrifice food quality to avoid close contact with a dominant animal, we suggest that the feeding space allowance should be at least 0.6m per cow whenever possible. However, even when space allowances are large, it is clear that some subordinate cows will still prefer to avoid proximity to dominant individuals.


Assuntos
Comportamento Alimentar , Animais , Bovinos/psicologia , Comportamento de Escolha , Indústria de Laticínios , Dominação-Subordinação , Comportamento Alimentar/psicologia , Feminino , Abrigo para Animais , Aprendizagem em Labirinto , Percepção Espacial
18.
Eur J Microbiol Immunol (Bp) ; 2(4): 282-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24265910

RESUMO

To assist international efforts to address major gaps in the availability and accessibility of quality diagnosis and treatment for multi-drug resistant tuberculosis, Médecins Sans Frontières has adapted an approach combining three sets of interlinked strategies: direct provision of medical care, operational research, and public health advocacy. The activities undertaken are reviewed each in turn, with stress on the ways that they impact upon and consolidate each other. In spite of new opportunities, including technologies which significantly improve diagnosis and new, more patient-centred approaches, a much broader international mobilization is needed in order to confront MDR-TB. It is also questionable as to whether existing technologies are successful enough to provide a solid basis for expanded national programs.

19.
Gut ; 59(12): 1635-42, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20926643

RESUMO

BACKGROUND AND AIMS: Increased efficiency of energy harvest, due to alterations in the gut microbiota (increased Firmicutes and decreased Bacteroidetes), has been implicated in obesity in mice and humans. However, a causal relationship is unproven and contributory variables include diet, genetics and age. Therefore, we explored the effect of a high-fat (HF) diet and genetically determined obesity (ob/ob) for changes in microbiota and energy harvesting capacity over time. METHODS: Seven-week-old male ob/ob mice were fed a low-fat diet and wild-type mice were fed either a low-fat diet or a HF-diet for 8 weeks (n=8/group). They were assessed at 7, 11 and 15 weeks of age for: fat and lean body mass (by NMR); faecal and caecal short-chain fatty acids (SCFA, by gas chromatography); faecal energy content (by bomb calorimetry) and microbial composition (by metagenomic pyrosequencing). RESULTS: A progressive increase in Firmicutes was confirmed in both HF-fed and ob/ob mice reaching statistical significance in the former, but this phylum was unchanged over time in the lean controls. Reductions in Bacteroidetes were also found in ob/ob mice. However, changes in the microbiota were dissociated from markers of energy harvest. Thus, although the faecal energy in the ob/ob mice was significantly decreased at 7 weeks, and caecal SCFA increased, these did not persist and faecal acetate diminished over time in both ob/ob and HF-fed mice, but not in lean controls. Furthermore, the proportion of the major phyla did not correlate with energy harvest markers. CONCLUSION: The relationship between the microbial composition and energy harvesting capacity is more complex than previously considered. While compositional changes in the faecal microbiota were confirmed, this was primarily a feature of high-fat feeding rather than genetically induced obesity. In addition, changes in the proportions of the major phyla were unrelated to markers of energy harvest which changed over time. The possibility of microbial adaptation to diet and time should be considered in future studies.


Assuntos
Dieta , Metabolismo Energético/fisiologia , Trato Gastrointestinal/microbiologia , Metagenoma/fisiologia , Obesidade/microbiologia , Envelhecimento/fisiologia , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Composição Corporal/fisiologia , Criopreservação , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Fezes/microbiologia , Trato Gastrointestinal/metabolismo , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Obesidade/fisiopatologia , Aumento de Peso/fisiologia
20.
Mol Genet Metab ; 100(1): 29-36, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20219402

RESUMO

Methylmalonic aciduria and homocystinuria, cblC type, is the most common inborn error of cellular vitamin B12 metabolism. We previously showed that the protein carrying the mutation responsible for late-onset cblC (MMACHC-R161Q), treatable with high dose OHCbl, is able to bind OHCbl with wild-type affinity, leaving undetermined the disease mechanism involved [Froese et al., Mechanism of responsiveness, Mol. Genet. Metab. (2009).]. To assess whether the mutation renders the protein unstable, we investigated the thermostability of the wild-type and mutant MMACHC proteins, either unbound or bound to different cobalamins (Cbl), using differential scanning fluorimetry. We found that MMACHC-wt and MMACHC-R161Q are both very thermolabile proteins in their apo forms, with melting temperatures (T(m)) of 39.3+/-1.0 and 37.1+/-0.7 degrees C, respectively; a difference confirmed by unfolding of MMACHC-R161Q but not MMACHC-wt by isothermal denaturation at 35 degrees C over 120 min. However, with the addition of OHCbl, MMACHC-wt becomes significantly stabilized (Delta T(m max)=8 degrees C, half-maximal effective ligand concentration, AC(50)=3 microM). We surveyed the effect of different cobalamins on the stabilization of the wild-type protein and found that AdoCbl was the most stabilizing, exerting a maximum increase in T(m) of approximately 16 degrees C, followed by MeCbl at approximately 13 degrees C, each evaluated at 50 microM cofactor. The other cobalamins stabilized in the order (CN)(2)Cbi>OHCbl>CNCbl. Interestingly, the AC(50)'s for AdoCbl, MeCbl, (CN)(2)Cbi and OHCbl were similar and ranged from 1-3 microM, which compares well with the K(d) of 6 microM for OHCbl [Froese et al., Mechanism of responsiveness, Mol. Genet. Metab. (2009).]. Unlike MMACHC-wt, the mutant protein MMACHC-R161Q is only moderately stabilized by OHCbl (Delta T(m max)=4 degrees C). The dose-response curve also shows a lower effectivity of OHCbl with respect to stabilization, with an AC(50) of 7 microM. MMACHC-R161Q showed the same order of stabilization as MMACHC-wt, but each cobalamin stabilized this mutant protein less than its wild-type counterpart. Additionally, MMACHC-R161Q had a higher AC(50) for each cobalamin form compared to MMACHC-wt. Finally, we show that MMACHC-R161Q is able to support the base-off transition for AdoCbl and CNCbl, indicating this mutant is not blocked in that respect. Taken together, our results suggest that protein stability, as well as propensity for ligand-induced stabilization, contributes to the disease mechanism in late-onset cblC disorder. Our results underscore the importance of cofactor stabilization of MMACHC and suggest that even small increases in the concentration of cobalamin complexed with MMACHC may have therapeutic benefit in children with the late-onset, vitamin responsive cblC disease.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Proteínas de Transporte/genética , Vitamina B 12/uso terapêutico , Idade de Início , Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Proteínas de Transporte/química , Cobamidas/química , Fluorometria , Homocistinúria/tratamento farmacológico , Homocistinúria/genética , Temperatura Alta , Humanos , Ácido Metilmalônico/urina , Oxirredutases , Desnaturação Proteica , Estabilidade Proteica , Vitamina B 12/análogos & derivados , Vitamina B 12/química , Vitamina B 12/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...