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1.
Bioengineering (Basel) ; 10(10)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37892943

RESUMO

It is generally accepted that the human abdominal wall comprises skin, subcutaneous tissues, muscles and their aponeuroses, and the parietal peritoneum. Understanding these layers and their mechanical properties provides valuable information to those designing procedural skills trainers, supporting surgical procedures (hernia repair), and engineering-based work (in silico simulation). However, there is little literature available on the mechanical properties of the abdominal wall in layers or as a composite in the context of designing a procedural skills trainer. This work characterizes the tensile properties of the human abdominal wall by layer and as a partial composite. Tissues were collected from fresh-never-frozen and fresh-frozen cadavers and tested in uniaxial tension at a rate of 5 mm/min until failure. Stress-strain curves were created for each sample, and the values for elastic moduli, ultimate tensile strength, and strain at failure were obtained. The experimental outcomes from this study demonstrated variations in tensile properties within and between tissues. The data also suggest that the tensile properties of composite abdominal walls are not additive. Ultimately, this body of work contributes to a deeper comprehension of these mechanical properties and will serve to enhance patient care, refine surgical interventions, and assist with more sophisticated engineering solutions.

2.
Food Nutr Bull ; 44(4): 229-239, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700715

RESUMO

BACKGROUND: Little is known about how the COVID-19 pandemic has affected food security and livelihoods in Sri Lanka. OBJECTIVE: This article aims to assess food insecurity, perceived effects of COVID-19, and coping mechanisms among agriculture-based households in rural Sri Lanka. METHODS: We used 2 rounds of panel data from phone surveys (n = 1057 households) conducted in 5 districts. Food insecurity (30-day recall), perceived impacts of COVID-19 (6-month recall), and coping mechanisms (6-month recall) were assessed using a household questionnaire. To assess food insecurity, we used the 8-item Food Insecurity Experience Scale. We tested for differences between T1 (baseline: December 2020-February 2021) and T2 (follow-up: July 2021-September 2021) and explored the association between food insecurity and the perceived effect of COVID-19 on income using a logistic regression model. RESULTS: Food insecurity was highly prevalent (T1: 75%, T2: 80%) but varied across districts. Most respondents were affected by COVID-19 and/or COVID-19-associated mitigation measures (T1: 84%, T2: 89%). Among affected households, commonly reported impacts included those on income (T1: 77%, T2: 76%), food costs (T1: 84%, T2: 83%), and travel (∼90% in both rounds). Agricultural activities were also adversely affected (T1: 64%, T2: 69%). About half of COVID-19-affected households reported selling livestock or assets to meet basic needs. Households whose income was impacted by COVID-19 were more likely to be food insecure (adjusted odds ratio: 2.56, P < .001). CONCLUSIONS: Households in rural Sri Lanka experienced food insecurity and livelihood disturbances during the COVID-19 pandemic. Additional surveys are needed to assess recovery post-COVID-19 and to understand if programs that support livelihoods have been protective.


METHOD: This original article used household level survey data from 2 rounds of phone surveys conducted in 5 districts of Sri Lanka.Using a household-level questionnaire, we recorded experience of food insecurity in the last 30 days, perceived impact of COVID-19, and adopted coping mechanism in the 6 months prior to the survey.We reported statistical means and tested for differences between 2 survey rounds.We also explored association between food insecurity and the perceived effect of COVID-19 on income. RESULTS: Household-level food insecurity was highly prevalent during the pandemic.Households perceived a negative effect of the pandemic on their income and employment sources.Households whose income was impacted by the pandemic were more likely to be food insecure. CONCLUSION: Agriculture-based households in rural Sri Lanka experienced food insecurity and livelihood disturbances during the COVID-19 pandemic.Additional research is needed to assess recovery post COVID-19 and to understand whether livelihood support programs have been protective.


Plain language titleFood Insecurity and Perceived Effects of COVID-19 on Livelihoods in Rural Sri LankaPlain language summaryBackground: Sustained levels of high food insecurity are associated with a range of negative health, nutrition, and well-being effects.The COVID-19 pandemic is expected to aggravate food insecurity and worsen the livelihood situation.Little is known about how the COVID-19 pandemic affected food security and livelihoods of agriculture-based households in rural Sri Lanka.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Sri Lanka/epidemiologia , Pandemias , Abastecimento de Alimentos , Insegurança Alimentar
3.
Food Nutr Bull ; 43(3): 251-270, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35610942

RESUMO

BACKGROUND: In 2016, a Peace Agreement, explicitly addressing the right to food, was signed, marking the end of more than 50 years of armed conflict and the longest war in the Americas. The expectation was that the years to follow would be marked by rapid social and political change, with the potential to improve food security. OBJECTIVES: (i) Ascertain changes in the prevalence of food insecurity in Colombia between 2016 and 2019; (ii) examine which population subgroups (eg, urban women, rural women, urban men, and rural men) were most vulnerable; and (iii) determine significant individual-level factors predicting food insecurity in these 2 years. METHODS: This study used the Gallup World Poll 2016 and 2019 nationally representative samples of Colombian adults aged 15 and older for the analyses (n ≈ 1000 per year). Food insecurity was measured using the Food Insecurity Experience Scale. Descriptive statistics and logistic regression analyses were conducted using IBM SPSS Complex Samples (version 26). RESULTS: Food insecurity in Colombia increased by 7 percentage points between 2016 and 2019 (from 33% to 40%); women living in rural areas in 2019 reported the highest prevalence (50%). Results from logistic analysis confirm low income, unemployment, and lack of social support were significant predictors of food insecurity in both years. In 2019, gender, low education, and lack of autonomy were also significant predictors. Further research on the determinants of food insecurity is necessary to inform Colombian policies and programs that address food insecurity. The urgency to act is more apparent than ever, given the country's worsening food security profile.


Assuntos
Abastecimento de Alimentos , Pobreza , Adulto , Colômbia , Feminino , Insegurança Alimentar , Humanos , Masculino , População Rural , Fatores Socioeconômicos
4.
Environ Sci Pollut Res Int ; 28(27): 36817-36827, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33710483

RESUMO

Tapado Glacier is a subtropical mountain glacier in the Coquimbo region of Chile that has been continuously retreating during the last 60 years due to diminishing precipitation rates and rising temperatures and likely due to a currently unknown influence from atmospheric pollutant deposition. Climatic and meteorological impacts on this, and other, Andean glacier have been previously studied; however, cryosphere changes driven by aerosols are still largely unknown. To contribute to the understanding of the origin of aerosols and their dispersion, this study aims to identify natural and anthropogenic sources of air pollution deposited on the Tapado Glacier (4500-5536 m a.s.l.) and their transport by using a receptor model (positive matrix factorization) together with the concentration of major ions as proxies of air pollution deposited on this glacier. This model's outcomes were complemented with daily wind backward trajectories computed for a whole year using the HYSPLYT meteorological model. Four sources were identified as the main contributors to major soluble ions in the Tapado surface snow. These sources are natural Aeolian dust (38%) from the Atacama Desert (including mining sites), natural weathered sulphates (27%), anthropogenic nitrates (25%), and coastal aerosols (10%). Coastal nitrate emissions and coastal aerosols are both sources with an important anthropogenic component, coming from La Serena and Coquimbo's coastal cities. The crustal components and sulphate profiles are similar to detritus dispersed from the glacier after wind erosion. Although the glacier is located over 4000 m above sea level, anthropogenic pollutants reached this location. However, their contributions were smaller compared to natural contaminants. Our findings can likely be extended to the nearest glaciers in Northern Chile, which have similar potential contaminant sources from cities, ports, and thriving mining activity. However, these findings may not be suitable for southern Chilean glaciers, which are closer to bigger cities and to smoke from residential heating prevalent in winter months and wildfires during the summer.


Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis/análise , Poluentes Atmosféricos/análise , Chile , Cidades , Monitoramento Ambiental , Camada de Gelo , Material Particulado/análise , Estações do Ano
5.
J Paediatr Child Health ; 57(2): 198-203, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32924233

RESUMO

AIM: The aim was to evaluate an educational video in educating doctors on the key messages and follow-up pathways following a first afebrile seizure presentation. A multidisciplinary expert team developed the video (http://www.pennsw.org.au/families/resources/first-seizure-pack-and-video) based on available evidence and best-practice. It contains a role-play between the parent/child and physician. It addresses: key messages to impart following a first seizure, seizure first aid, safety messages including necessary precautions post-discharge, contents of the First Seizure Pack for families, follow-up pathway and issues for discussion with the paediatrician at a later appointment. METHODS: Paediatric/Emergency department (ED) trainees across three Australian sites were recruited during terms 1 and 2, 2019. A repeated measures design was used. Multilevel modelling analyses were performed. The primary outcome was clinician knowledge. Secondary outcomes were confidence in answering questions and counselling families. Qualitative data on the utility, strengths and weaknesses of the video were evaluated. RESULTS: A total of 127 participants consented, one withdrew prior to commencing. A total of 126 baseline surveys, 115 follow-up surveys and 45 1-month follow-up surveys were returned. Viewing the video significantly improved knowledge of key messages at immediate follow-up (P < 0.001) and 1-month follow-up (P = 0.048). Likewise, confidence was significantly improved; 96.5% of responders found the video useful, 90.3% were likely to use the resource in the future and 82% would change their approach to counselling. Most liked aspects of the resource were clarity/conciseness of the information (n = 70) and comprehensiveness (n = 38). CONCLUSION: This education video significantly improved clinician knowledge and confidence in counselling families following first seizure.


Assuntos
Assistência ao Convalescente , Médicos , Austrália , Criança , Humanos , Alta do Paciente , Convulsões
6.
Pediatr Neurol ; 100: 92-96, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31376926

RESUMO

BACKGROUND: Acute hemorrhagic leukoencephalopathy is a rare encephalopathy of unknown etiology, causing fulminant, hemorrhagic central nervous system demyelination with high mortality. It is unclear whether acute hemorrhagic leukoencephalopathy is an entirely distinct entity from acute disseminated encephalomyelitis. PATIENTS AND METHODS: We report two patients with rapidly progressive neurological illness resulting in raised intracranial pressure and coma, with biopsy-proven acute hemorrhagic leukoencephalopathy (perivascular hemorrhages and demyelination, predominantly neutrophil infiltrates). RESULTS: Acute cerebrospinal fluid showed pronounced T cell-associated cytokine elevation (interleukins 6, 8, and 17A) and CCL2 or CCL3, higher than in patients with acute disseminated encephalomyelitis, but no B cell-associated cytokine elevation. CONCLUSION: Improved understanding of the immune process may provide rationale for use of anticytokine biologic agents.


Assuntos
Citocinas/líquido cefalorraquidiano , Leucoencefalite Hemorrágica Aguda , Adolescente , Humanos , Leucoencefalite Hemorrágica Aguda/líquido cefalorraquidiano , Leucoencefalite Hemorrágica Aguda/imunologia , Leucoencefalite Hemorrágica Aguda/patologia , Leucoencefalite Hemorrágica Aguda/fisiopatologia , Imageamento por Ressonância Magnética , Masculino
7.
Public Health Nutr ; : 1-11, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30319089

RESUMO

OBJECTIVE: To simulate impact of Ca supplementation on estimated total Ca intakes among women in a population with low dietary Ca intakes, using WHO recommendations: 1·5-2·0 g elemental Ca/d during pregnancy to prevent pre-eclampsia. DESIGN: Single cross-sectional 24 h dietary recall data were adjusted using IMAPP software to simulate proportions of women who would meet or exceed the Estimated Average Requirement (EAR) and Tolerable Upper Intake Level (UL) assuming full or partial adherence to WHO guidelines. SETTING: Nationally and regionally representative data, Ethiopia's 'lean' season 2011. SUBJECTS: Women 15-45 years (n 7908, of whom 492 pregnant). RESULTS: National mean usual Ca intake was 501 (sd 244) mg/d. Approximately 89, 91 and 96 % of all women, pregnant women and 15-18 years, respectively, had dietary Ca intakes below the EAR. Simulating 100 % adherence to 1·0, 1·5 and 2·0 g/d estimated nearly all women (>99 %) would meet the EAR, regardless of dosage. Nationally, supplementation with 1·5 and 2·0 g/d would result in intake exceeding the UL in 3·7 and 43·2 % of women, respectively, while at 1·0 g/d those exceeding the UL would be <1 % (0·74 %) except in one region (4·95 %). CONCLUSIONS: Most Ethiopian women consume insufficient Ca, increasing risk of pre-eclampsia. Providing Ca supplements of 1·5-2·0 g/d could result in high proportions of women exceeding the UL, while universal consumption of 1·0 g/d would meet requirements with minimal risk of excess. Appropriately tested screening tools could identify and reduce risk to high Ca consumers. Research on minimum effective Ca supplementation to prevent pre-eclampsia is also needed to determine whether lower doses could be recommended.

9.
Neuroimage Clin ; 9: 206-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26413479

RESUMO

BACKGROUND: Our understanding of the effect of ataxia-telangiectasia mutated gene mutations on brain structure and function is limited. In this study, white matter motor pathway integrity was investigated in ataxia telangiectasia patients using diffusion MRI and probabilistic tractography. METHODS: Diffusion MRI were obtained from 12 patients (age range: 7-22 years, mean: 12 years) and 12 typically developing age matched participants (age range 8-23 years, mean: 13 years). White matter fiber tracking and whole tract statistical analyses were used to assess quantitative fractional anisotropy and mean diffusivity differences along the cortico-ponto-cerebellar, cerebellar-thalamo-cortical, somatosensory and lateral corticospinal tract length in patients using a linear mixed effects model. White matter tract streamline number and apparent fiber density in patient and control tracts were also assessed. RESULTS: Reduced fractional anisotropy along all analyzed patient tracts were observed (p < 0.001). Mean diffusivity was significantly elevated in anterior tract locations but was reduced within cerebellar peduncle regions of all patient tracts (p < 0.001). Reduced tract streamline number and tract volume in the left and right corticospinal and somatosensory tracts were observed in patients (p < 0.006). In addition, reduced apparent fiber density in the left and right corticospinal and right somatosensory tracts (p < 0.006) occurred in patients. CONCLUSIONS: Whole tract analysis of the corticomotor, corticospinal and somatosensory pathways in ataxia telangiectasia showed significant white matter degeneration along the entire length of motor circuits, highlighting that ataxia-telangiectasia gene mutation impacts the cerebellum and multiple other motor circuits in young patients.


Assuntos
Ataxia Telangiectasia/patologia , Encéfalo/patologia , Substância Branca/patologia , Adolescente , Adulto , Criança , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Vias Eferentes/patologia , Feminino , Humanos , Masculino , Adulto Jovem
10.
J Paediatr Child Health ; 51(8): 802-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25656498

RESUMO

AIM: Ataxia-telangiectasia (A-T) is a rare genomic syndrome resulting in severe disability. Chronic childhood disorders can profoundly influence growth and development. Nutrition-related issues in A-T are not well described, and there are no nutritional guidelines. This study investigated the nutrition-related characteristics and behaviours of Australian A-T patients attending a national clinic. METHODS: A cross-sectional analysis of 13 A-T patients (nine females; aged: 4-23 years): nutritional status was assessed by anthropometric and body cell mass (BCM) calculations. Parents reported their child's diet history and physical and behavioural factors that affect nutrition including fatigue and need for assistance. RESULTS: Ten (77%) had short stature (height for age z scores <-1), and seven (54%) were underweight for height (weight/height z scores <-1). Significant malnutrition (BCM z scores <-2) was detected in nine (69%) including the one adult who was severely malnourished. Malnutrition increased significantly with age (BCM for height z scores and age, r = -0.937, P < 0.001). Eight (62%) patients ate poorly compared with estimated energy requirement for weight. Poor diet quality was characterised by high fat and sugar choices. Parents reported significant nutritional barriers as chronic tiredness and the need for care giver assistance with meals. CONCLUSIONS: This study confirms profound malnutrition in Australian A-T patients. Poor intakes and diet quality suggest the need for early nutrition intervention. Ongoing support for families and early discussions on tube feeding are required to address changing needs in childhood and likely nutritional decline into adulthood. A prospective study is required to assess feasibility and effectiveness of nutrition interventions in young people with A-T.


Assuntos
Ataxia Telangiectasia/complicações , Desnutrição/etiologia , Estado Nutricional , Adolescente , Austrália , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos Transversais , Fadiga/etiologia , Comportamento Alimentar , Feminino , Humanos , Masculino , Adulto Jovem
11.
Mov Disord ; 29(10): 1289-98, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25042086

RESUMO

Magnetic resonance imaging (MRI) research in identifying altered brain structure and function in ataxia-telangiectasia, an autosomal recessive neurodegenerative disorder, is limited. Diffusion-weighted MRI were obtained from 11 ataxia telangiectasia patients (age range, 7-22 years; mean, 12 years) and 11 typically developing age-matched participants (age range, 8-23 years; mean, 13 years). Gray matter volume alterations in patients were compared with those of healthy controls using voxel-based morphometry, whereas tract-based spatial statistics was employed to elucidate white matter microstructure differences between groups. White matter microstructure was probed using quantitative fractional anisotropy and mean diffusivity measures. Reduced gray matter volume in both cerebellar hemispheres and in the precentral-postcentral gyrus in the left cerebral hemisphere was observed in ataxia telangiectasia patients compared with controls (P < 0.05, corrected for multiple comparisons). A significant reduction in fractional anisotropy in the cerebellar hemispheres, anterior/posterior horns of the medulla, cerebral peduncles, and internal capsule white matter, particularly in the left posterior limb of the internal capsule and corona radiata in the left cerebral hemisphere, was observed in patients compared with controls (P < 0.05). Mean diffusivity differences were observed within the left cerebellar hemisphere and the white matter of the superior lobule of the right cerebellar hemisphere (P < 0.05). Cerebellum-localized gray matter changes are seen in young ataxia telangiectasia patients along with white matter tract degeneration projecting from the cerebellum into corticomotor regions. The lack of cortical involvement may reflect early-stage white matter motor pathway degeneration within young patients.


Assuntos
Ataxia Telangiectasia/patologia , Cerebelo/patologia , Córtex Motor/patologia , Vias Neurais/patologia , Adolescente , Anisotropia , Estudos de Casos e Controles , Criança , Imagem de Difusão por Ressonância Magnética , Movimentos Oculares/fisiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Índice de Gravidade de Doença , Substância Branca/patologia , Adulto Jovem
12.
Cerebellum ; 13(4): 521-30, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24683014

RESUMO

The human genetic disorder ataxia telangiectasia (A-T) is characterised by neurodegeneration, immunodeficiency, radiosensitivity, cell cycle checkpoint defects, genomic instability and cancer predisposition. Progressive cerebellar ataxia represents the most debilitating aspect of this disorder. At present, there is no therapy available to cure or prevent the progressive symptoms of A-T. While it is possible to alleviate some of the symptoms associated with immunodeficiency and deficient lung function, neither the predisposition to cancer nor the progressive neurodegeneration can be prevented. Significant effort has focused on improving our understanding of various clinical, genetic and immunological aspects of A-T; however, little attention has been directed towards identifying altered brain structure and function using MRI. To date, most imaging studies have reported radiological anomalies in A-T. This review outlines the clinical and biological features of A-T along with known radiological imaging anomalies. In addition, we briefly discuss the advent of high-resolution MRI in conjunction with diffusion-weighted imaging, which enables improved investigation of the microstructural tissue environment, giving insight into the loss in integrity of motor networks due to abnormal neurodevelopmental or progressive neurodegenerative processes. Such imaging approaches have yet to be applied in the study of A-T and could provide important new information regarding the relationship between mutation of the ataxia telangiectasia mutated (ATM) gene and the integrity of motor circuitry.


Assuntos
Ataxia Telangiectasia/diagnóstico , Encéfalo/patologia , Diagnóstico por Imagem , Ataxia Telangiectasia/fisiopatologia , Humanos , Estresse Oxidativo/fisiologia
13.
Mov Disord ; 29(1): 117-22, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24115338

RESUMO

BACKGROUND: Movement disorder relapses after herpes simplex virus 1 (HSV1) encephalitis have been hypothesized to be secondary to postviral autoimmunity. Recently, a proportion of patients with HSV1 encephalitis (HSE) were shown to produce autoantibodies against N-methyl-D-aspartate receptor (NMDAR). METHODS: We measured autoantibodies against NMDAR and dopamine-2 receptor (D2R) expressed at the cell surface in the stored acute serum of 9 children with HSE, 3 of whom had a relapsing course with chorea. RESULTS: The 3 patients with chorea had elevated autoantibodies against NMDAR (n = 1), D2R (n = 1), or both (n = 1), whereas patients without chorea were negative (n = 6). The prospectively identified patient with chorea and NMDAR autoantibodies improved after early treatment with steroids, intravenous immunoglobulin, and cyclophosphamide, with reduction in serum NMDAR antibody titers. CONCLUSIONS: These autoantibody findings lend support to the autoimmune hypothesis and the early use of immune suppression in post-HSE chorea.


Assuntos
Autoanticorpos/sangue , Coreia/imunologia , Encefalite por Herpes Simples/imunologia , Receptores de Dopamina D2/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Criança , Pré-Escolar , Coreia/sangue , Coreia/complicações , Encefalite por Herpes Simples/sangue , Encefalite por Herpes Simples/complicações , Feminino , Humanos , Lactente , Masculino , Recidiva
14.
Hum Mol Genet ; 22(12): 2495-509, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23474819

RESUMO

The autosomal recessive disorder ataxia-telangiectasia (A-T) is characterized by genome instability, cancer predisposition and neurodegeneration. Although the role of ataxia-telangiectasia mutated (ATM) protein, the protein defective in this syndrome, is well described in the response to DNA damage, its role in protecting the nervous system is less clear. We describe the establishment and characterization of patient-specific stem cells that have the potential to address this shortcoming. Olfactory neurosphere (ONS)-derived cells were generated from A-T patients, which expressed stem cell markers and exhibited A-T molecular and cellular characteristics that included hypersensitivity to radiation, defective radiation-induced signaling and cell cycle checkpoint defects. Introduction of full-length ATM cDNA into these cells corrected defects in the A-T cellular phenotype. Gene expression profiling and pathway analysis revealed defects in multiple cell signaling pathways associated with ATM function, with cell cycle, cell death and DNA damage response pathways being the most significantly dysregulated. A-T ONS cells were also capable of differentiating into neural progenitors, but they were defective in neurite formation, number of neurites and length of these neurites. Thus, ONS cells are a patient-derived neural stem cell model that recapitulate the phenotype of A-T, do not require genetic reprogramming, have the capacity to differentiate into neurons and have potential to delineate the neurological defect in these patients.


Assuntos
Ataxia Telangiectasia/fisiopatologia , Neurônios/citologia , Condutos Olfatórios/citologia , Células-Tronco/citologia , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/metabolismo , Ataxia Telangiectasia/patologia , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Diferenciação Celular , Células Cultivadas , Criança , Feminino , Humanos , Lactente , Masculino , Modelos Biológicos , Mucosa , Neurônios/metabolismo , Neurônios/patologia , Fenótipo , Células-Tronco/metabolismo , Células-Tronco/patologia
15.
J Biol Chem ; 287(34): 28975-85, 2012 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-22700964

RESUMO

Hereditary hyperekplexia or startle disease is characterized by an exaggerated startle response, evoked by tactile or auditory stimuli, leading to hypertonia and apnea episodes. Missense, nonsense, frameshift, splice site mutations, and large deletions in the human glycine receptor α1 subunit gene (GLRA1) are the major known cause of this disorder. However, mutations are also found in the genes encoding the glycine receptor ß subunit (GLRB) and the presynaptic Na(+)/Cl(-)-dependent glycine transporter GlyT2 (SLC6A5). In this study, systematic DNA sequencing of SLC6A5 in 93 new unrelated human hyperekplexia patients revealed 20 sequence variants in 17 index cases presenting with homozygous or compound heterozygous recessive inheritance. Five apparently unrelated cases had the truncating mutation R439X. Genotype-phenotype analysis revealed a high rate of neonatal apneas and learning difficulties associated with SLC6A5 mutations. From the 20 SLC6A5 sequence variants, we investigated glycine uptake for 16 novel mutations, confirming that all were defective in glycine transport. Although the most common mechanism of disrupting GlyT2 function is protein truncation, new pathogenic mechanisms included splice site mutations and missense mutations affecting residues implicated in Cl(-) binding, conformational changes mediated by extracellular loop 4, and cation-π interactions. Detailed electrophysiology of mutation A275T revealed that this substitution results in a voltage-sensitive decrease in glycine transport caused by lower Na(+) affinity. This study firmly establishes the combination of missense, nonsense, frameshift, and splice site mutations in the GlyT2 gene as the second major cause of startle disease.


Assuntos
Doenças Genéticas Inatas , Proteínas da Membrana Plasmática de Transporte de Glicina , Glicina/metabolismo , Mutação , Proteínas do Tecido Nervoso , Doenças Neurodegenerativas , Animais , Análise Mutacional de DNA , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/metabolismo , Glicina/genética , Proteínas da Membrana Plasmática de Transporte de Glicina/genética , Proteínas da Membrana Plasmática de Transporte de Glicina/metabolismo , Heterozigoto , Homozigoto , Humanos , Transporte de Íons/genética , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Estrutura Terciária de Proteína , Receptores de Glicina/genética , Receptores de Glicina/metabolismo , Xenopus laevis
16.
Patient Educ Couns ; 78(2): 177-83, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19647970

RESUMO

OBJECTIVE: Our aim was to develop a measurement which enables research into the interdependent nature of clinical encounters. The prime objective was to develop an instrument capable of assessing the extent to which patients have been involved in (shared) decision making from two viewpoints-that of the patient and the clinician. METHODS: To develop an initial 'dyadic OPTION' instrument, the twelve original third-person items were drafted in passive, first person plural forms. Using this version initially, three rounds of cognitive debriefing interviews were held. These were audio-recorded and analysed at the end of each round and the results used to revise the dyadic OPTION scale. RESULTS: It was possible to modify the observer OPTION instrument into an instrument for completion by both clinicians and patients after a dyadic interaction. Cognitive debriefing revealed five areas of interpretative difficulty. Each item of the observer OPTION scale underwent modification in order to develop a dyadic version of the scale. CONCLUSIONS: The dyadic OPTION scale is acceptable and comprehensible by both clinicians and public respondents. Cognitive debriefing adapted and refined an existing scale and provided confidence that the core constructs of the scale (perceived involvement in decisions making) were understood. PRACTICE IMPLICATIONS: Further validation of the dyadic OPTION scale is required prior to its use in research settings.


Assuntos
Tomada de Decisões , Participação do Paciente , Assistência Centrada no Paciente , Relações Médico-Paciente , Psicometria/instrumentação , Adolescente , Adulto , Idoso , Medicina de Família e Comunidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
18.
Brain Res ; 1179: 79-88, 2007 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-17936737

RESUMO

Intrauterine growth restriction (IUGR) can increase susceptibility to perinatal hypoxic brain injury for reasons that are unknown. Previous studies of the neonatal IUGR brain have suggested that the cerebral mitochondrial capacity is reduced but the glycolytic capacity increased relative to normal weight (NW) neonates. In view of these two factors, we hypothesized that the generation of brain lactate during a mild hypoxic insult would be greater in neonatal IUGR piglets compared to NW piglets. Brain lactate/N-acetylaspartate (NAA) ratios and apparent diffusion coefficients (ADCs) were determined by proton magnetic resonance spectroscopy and imaging of the brain before, during and after hypoxia in seven neonatal piglets with asymmetric IUGR and six NW piglets. During hypoxia, IUGR piglets had significantly higher brain lactate/NAA ratios than NW piglets (P=0.046). The lactate response in the IUGR piglets correlated inversely with apoptosis in the thalamus and frontal cortex of the brain measured 4 h post hypoxia (Pearson's r=0.86, P<0.05). Apoptosis in IUGR piglets with high brain lactate was similar to that in the NW piglets whereas IUGR piglets with low brain lactate had significantly higher apoptosis than NW piglets (P=0.019). ADCs in the high lactate IUGR piglets were significantly lower during hypoxia than in all the other piglets. This signifies increased diffusion of water into brain cells during hypoxia, possibly in response to increased intracellular osmolality caused by high intracellular lactate concentrations. These findings support previous studies showing increased susceptibility to hypoxic brain injury in IUGR neonates but suggest that increased glycolysis during hypoxia confers neuroprotection in some IUGR piglets.


Assuntos
Animais Recém-Nascidos/fisiologia , Química Encefálica/fisiologia , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/patologia , Hipóxia Encefálica/patologia , Ácido Láctico/metabolismo , Animais , Apoptose/fisiologia , Peso ao Nascer/fisiologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Contagem de Células , Imagem de Difusão por Ressonância Magnética , Metabolismo Energético/fisiologia , Lobo Frontal/crescimento & desenvolvimento , Lobo Frontal/patologia , Hipóxia Encefálica/metabolismo , Processamento de Imagem Assistida por Computador , Fígado/crescimento & desenvolvimento , Fígado/patologia , Espectroscopia de Ressonância Magnética , Tamanho do Órgão/fisiologia , Córtex Pré-Frontal/patologia , Suínos , Tálamo/patologia
19.
Brain Res ; 1098(1): 19-25, 2006 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-16808906

RESUMO

Uteroplacental vascular insufficiency in humans is a common cause of intrauterine growth restriction (IUGR) and is associated with an increased incidence of perinatal asphyxia and neurodevelopmental disorders compared to normal weight newborns. Experimental models that provide an opportunity to analyze the pathogenesis of these relationships are limited. Here, we used neonatal pigs from large litters in which there were piglets of normal birth weight (for controls) and of low birth weight (for uteroplacental vascular insufficiency). Hypoxia was induced in paired littermates by reducing the fraction of inspired oxygen to 4% for 25 min. Brain tissue was collected 4 h post-hypoxia. Cerebral levels of apoptosis were quantified morphologically and verified with caspase-3 activity and TUNEL. Expression of Bcl-2, Bcl-XL and Bax proteins was investigated using immunohistochemistry. Cellular positivity for Bcl-2 was consistently higher in the non-apoptotic white matter of the hypoxic IUGR animals compared with their littermates and reached significance at P < 0.05 in several pairs of littermates. Alterations in Bax showed a trend towards higher expression in the hypoxic IUGR littermates but rarely reached significance. The IUGR piglets showed a significantly greater amount of apoptosis in response to the hypoxia than the normal weight piglets, suggesting an increased vulnerability to apoptosis in the IUGR piglets.


Assuntos
Animais Recém-Nascidos/fisiologia , Apoptose/fisiologia , Retardo do Crescimento Fetal/fisiopatologia , Hipóxia Encefálica/etiologia , Hipóxia Encefálica/patologia , Placenta/irrigação sanguínea , Útero/irrigação sanguínea , Animais , Peso Corporal/fisiologia , Encéfalo/patologia , Contagem de Células , Feminino , Lobo Frontal/patologia , Genes bcl-2/fisiologia , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Isquemia/fisiopatologia , Fígado/patologia , Tamanho do Órgão/fisiologia , Gravidez , Fluxo Sanguíneo Regional/fisiologia , Suínos , Tálamo/patologia
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