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1.
Animal ; 17 Suppl 3: 100832, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37210231

RESUMO

With more efficient utilisation of dietary nutrients and energy, diversified production systems, modifications of diet composition with respect to feedstuffs included and the use of free amino acids, the negative impact of animal food production on the environment and climate can be reduced. Accurate requirements for nutrients and energy for animals with differing physiological needs, and the use of robust and accurate feed evaluation systems are key for more efficient feed utilisation. Data on CP and amino acid requirements in pigs and poultry indicate that it should be possible to implement indispensable amino acid-balanced diets with low- or reduced-protein content without any reduction in animal performance. Potential feed resources, not competing with human food security, can be derived from the traditional food- and agroindustry, such as various waste streams and co-products of different origins. In addition, novel feedstuffs emerging from aquaculture, biotechnology and innovative new technologies may have potential to provide the lack of indispensable amino acids in organic animal food production. High fibre content is a nutritional limitation of using waste streams and co-products as feed for monogastric animals as it is associated with decreased nutrient digestibility and reduced dietary energy values. However, minimum levels of dietary fibre are needed to maintain the normal physiological function of the gastro-intestinal tract. Moreover, there may be positive effects of fibre in the diet such as improved gut health, increased satiety, and an overall improvement of behaviour and well-being.


Assuntos
Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Suínos , Animais , Humanos , Ração Animal/análise , Nutrientes , Dieta/veterinária , Aves Domésticas/metabolismo , Aminoácidos/metabolismo , Digestão
2.
Ann Oncol ; 33(8): 750-768, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35809752

RESUMO

Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue-based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false-negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease or molecular relapse, has high evidence of clinical validity in anticipating future relapse in many cancers. Molecular residual disease/molecular relapse detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations before clinical progression, and in screening asymptomatic people for cancer. Recommendations for reporting of results, future development of ctDNA assays and future clinical research are made.


Assuntos
DNA Tumoral Circulante , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Humanos , Mutação , Recidiva Local de Neoplasia , Medicina de Precisão/métodos
3.
Curr Environ Health Rep ; 8(3): 235-244, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33982149

RESUMO

PURPOSE OF REVIEW: To identify important home care (HC) aide occupational safety and health (OSH) hazards and examine how addressing these can improve aide health and the delivery of HC services overall. Specifically, this review seeks to answer: Why is HC aide OSH important? What are the most significant OSH challenges? How can improving HC aide OSH also improve the safety and health of their clients? What implications do the findings have for future research? RECENT FINDINGS: HC is one of the fastest growing US industries. Aides comprise its largest workforce and are increasingly needed to care for the rapidly aging population. There is an aide shortage due in part to instabilities in HC work organization and to serious job-specific hazards, resulting in aides losing work time. Recent social, economic, and technological factors are rapidly changing the nature of HC work, creating OSH hazards similar to those found in nursing homes. At the same time, aides are experiencing social and economic inequities that increase their vulnerability to OSH hazards. These hazards are also a burden on employers who are challenged to recruit, retain, and train aides. OSH injuries and illness interrupt the continuity of care delivery to clients. Many OSH hazards also put HC clients and families at risk. A new framework and methodologies are needed to assess aide and client safety together in order to guide future HC research, policies, and practices. Government, industry, and labor commitment is needed to fund and coordinate a comprehensive, multidisciplinary research program.


Assuntos
Envelhecimento Saudável , Serviços de Assistência Domiciliar , Visitadores Domiciliares , Saúde Ocupacional , Idoso , Humanos , Recursos Humanos
4.
J Occup Environ Hyg ; 18(6): 276-287, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34004120

RESUMO

Home care (HC) aide visits to clients' homes often involve cleaning and disinfecting (C&D) bathrooms. Some ingredients in C&D household products are associated with respiratory illness, including sodium hypochlorite (bleach) and quaternary ammonium compounds (quats). "Green" products may be safer for the environment, however there are limited quantitative evaluations of their respiratory risks. This study assessed airborne concentrations and time profiles of total volatile organic compounds (TVOC) and chlorine generated during typical bathroom cleaning performed by aides using conventional and green products. Aides performed cleaning tasks in a simulated residential bathroom constructed in an environmental air sampling laboratory. A balanced experimental design involved each aide coming to the lab for four visits during which she performed two 20-min cleaning sessions using one of three C&D products (bleach-based, 1-5% sodium hypochlorite by weight; quats-based, 0.1-1% by weight quaternary ammonium compounds; and "green," 0.05% by weight thymol, a component of botanical thyme oil) or distilled water as a control. TVOC and chlorine direct reading instruments were attached to aides with sample inlets located in the breathing zone. Ten-second averages of TVOC and chlorine gas concentrations and instantaneous peak concentrations were recorded for the sessions' duration. TVOC concentrations by methods of C&D application (spraying, streaming, wiping) also were evaluated. The study completed 169 air sampling sessions with 22 aides. The quats-based product generated more than twice the average TVOC concentrations (mean = 1,210 ppb) than the bleach-based (mean = 593 ppb) or green (mean = 498 ppb) products. Each product generated TVOC concentrations that rose rapidly within the first few minutes of application. Spraying produced the highest TVOC exposures, wiping the lowest. Thirteen aides (65%) experienced peak chlorine exposures above the OSHA PEL ceiling limit (1 ppm) when using the bleach-based product. HC aides may experience respiratory hazards from use of conventional or green C&D products formulated with bleach or other respiratory irritants and sprayed in small, poorly ventilated spaces typical of bathrooms. Spraying should be avoided.


Assuntos
Visitadores Domiciliares , Compostos Orgânicos Voláteis , Cloro , Feminino , Humanos , Projetos de Pesquisa , Banheiros
5.
J Assist Reprod Genet ; 37(9): 2137-2150, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32671735

RESUMO

PURPOSE: Our purpose was to identify human ovarian extracellular matrix (ECM) components that would support in vitro culture of human ovarian tissue and be compatible with possible future clinical applications. We characterized ovarian expression of laminins and selected three laminin tripeptides for culture experiments to be compared with Matrigel, an undefined and animal-based mixture of ECM components. METHODS: Expression of the 12 laminin genes was determined on transcript and protein levels using cortical tissue samples (n = 6), commercial ovary RNA (n = 1), follicular fluid granulosa cells (n = 20), and single-cell RNA-sequencing data. Laminin 221 (LN221), LN521, LN511, and their mixture were chosen for a 7-day culture experiment along with Matrigel using tissue from 17 patients. At the end of the culture, follicles were evaluated by scoring and counting from serial tissue sections, apoptosis measured using in situ TUNEL assay, proliferation by Ki67 staining, and endocrine function by quantifying steroids in culture media using UPLC-MS/MS. RESULTS: Approximately half of the cells in ovarian cortex expressed at least one laminin gene. The overall most expressed laminin α-chains were LAMA2 and LAMA5, ß-chains LAMB1 and LAMB2, and γ-chain LAMC1. In culture experiments, LN221 enhanced follicular survival compared with Matrigel (p < 0.001), whereas tissue cultured on LN521 had higher proportion of secondary follicles (p < 0.001). LN511 and mixture of laminins did not support the cultures leading to lower follicle densities and higher apoptosis. All cultures produced steroids and contained proliferating cells. CONCLUSIONS: LN221 and LN521 show promise in providing xeno-free growth substrates for human ovarian tissue cultures, which may help in further development of folliculogenesis in vitro for clinical practices. The system could also be used for identification of adverse effects of chemicals in ovaries.


Assuntos
Matriz Extracelular/química , Laminina/farmacologia , Ovário/crescimento & desenvolvimento , Técnicas de Cultura de Tecidos , Adulto , Cromatografia Líquida , Colágeno/química , Colágeno/farmacologia , Meios de Cultura/farmacologia , Combinação de Medicamentos , Matriz Extracelular/genética , Feminino , Células da Granulosa , Humanos , Laminina/química , Pessoa de Meia-Idade , Folículo Ovariano , Ovário/efeitos dos fármacos , Proteoglicanas/química , Proteoglicanas/farmacologia , RNA-Seq , Análise de Célula Única , Espectrometria de Massas em Tandem
7.
J Clin Psychol ; 73(12): 1612-1628, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28249107

RESUMO

OBJECTIVE: We conducted a controlled randomized preliminary trial of a modified dissonance-based eating disorder program (n = 24) compared to an assessment-only control condition (n = 23) via a longitudinal design (baseline, postintervention, 2-month follow-up) in a community sample of women (N = 47) with clinical (n = 22) and subclinical (n = 25) eating disorder symptoms. METHOD: The traditional content of the Body Project, a dissonance-based eating disorder prevention program, was modified to include verbal, written, and behavioral exercises designed to dissuade self-objectification and maladaptive social comparison. Women with clinical and subclinical symptoms were included in the target audience to investigate both the treatment and the indicated prevention utility of the modified dissonance program. Body dissatisfaction, self-esteem, self-objectification, thin-ideal internalization, maladaptive social comparison, trait anxiety, and eating disorder symptoms were evaluated in the control and the modified dissonance condition at baseline, postintervention, and 2-month follow-up. RESULTS: We predicted a statistically significant 2 (condition: control, modified dissonance) x 3 (time: baseline, postintervention, 2-month follow-up) interaction in the mixed factorial multivariate analyses of variance results. Results confirmed this hypothesis. Eating disorder risk factors and symptoms decreased significantly among participants in the modified dissonance condition at postintervention and 2-month follow-up compared to baseline; symptom improvement was greater among participants in the modified compared to the control condition. A secondary analysis indicated symptom improvement did not vary as a function of symptom status (clinical, subclinical), suggesting the program is efficacious in both indicated prevention and treatment applications. CONCLUSION: Results provide preliminary support for the modified dissonance program.


Assuntos
Imagem Corporal , Terapia Cognitivo-Comportamental/métodos , Dissonância Cognitiva , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Avaliação de Resultados em Cuidados de Saúde , Autoimagem , Percepção Social , Adolescente , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Transtornos da Alimentação e da Ingestão de Alimentos/prevenção & controle , Feminino , Seguimentos , Humanos , Projetos Piloto , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
8.
Urol Oncol ; 35(3): 120, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28215847

RESUMO

BACKGROUND: The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone. METHODS: The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50 to 69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms [232 SNPs], and clinical variables [age, family, history, previous prostate biopsy, prostate exam]), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com, number ISRCTN84445406. FINDINGS: The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (P<0.0001), the area under the curve was 0·56 (95% CI: 0·55-0·60) with PSA alone and 0·74 (95% CI: 0·72-0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (P<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of≥3ng/ml to diagnose high-risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI: 24-39) and could avoid 44% (35-54) of benign biopsies. INTERPRETATION: The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes. FUNDING: Stockholm County Council (Stockholms Läns Landsting).


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata , Idoso , Biópsia , Detecção Precoce de Câncer , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Suécia
9.
Leukemia ; 31(10): 2029-2036, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28167833

RESUMO

Risk stratification of acute myeloid leukemia (AML) patients needs improvement. Several AML risk classification models based on somatic mutations or gene-expression profiling have been proposed. However, systematic and independent validation of these models is required for future clinical implementation. We performed whole-transcriptome RNA-sequencing and panel-based deep DNA sequencing of 23 genes in 274 intensively treated AML patients (Clinseq-AML). We also utilized the The Cancer Genome Atlas (TCGA)-AML study (N=142) as a second validation cohort. We evaluated six previously proposed molecular-based models for AML risk stratification and two revised risk classification systems combining molecular- and clinical data. Risk groups stratified by five out of six models showed different overall survival in cytogenetic normal-AML patients in the Clinseq-AML cohort (P-value<0.05; concordance index >0.5). Risk classification systems integrating mutational or gene-expression data were found to add prognostic value to the current European Leukemia Net (ELN) risk classification. The prognostic value varied between models and across cohorts, highlighting the importance of independent validation to establish evidence of efficacy and general applicability. All but one model replicated in the Clinseq-AML cohort, indicating the potential for molecular-based AML risk models. Risk classification based on a combination of molecular and clinical data holds promise for improved AML patient stratification in the future.


Assuntos
Perfilação da Expressão Gênica , Leucemia Mieloide Aguda/genética , Modelos Biológicos , Medição de Risco/métodos , Análise de Sequência de DNA , Transcriptoma , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/química , Estudos de Coortes , Análise Mutacional de DNA , DNA de Neoplasias/genética , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/classificação , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , RNA Neoplásico/genética , Adulto Jovem
10.
Scand J Surg ; 106(2): 133-138, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27431978

RESUMO

BACKGROUND AND AIMS: Ulcerative colitis increases the risk of developing colorectal cancer. Colonoscopic surveillance is recommended although there are no randomized trials evaluating the efficacy of such a strategy. This study is an update of earlier studies from an ongoing colonoscopic surveillance program. MATERIAL AND METHODS: All patients with ulcerative colitis were invited to the surveillance program that started in 1977 at Örnsköldsvik Hospital, located in the northern part of Sweden. Five principal endoscopists performed the colonoscopies and harvested mucosal sampling for histopathological evaluation. Some 323 patients from the defined catchment area were studied from 1977 to 2014. At the end of the study period, 130 patients, including those operated on, had had total colitis for more than 10 years. RESULTS: In total, 1481 colonoscopies were performed on 323 patients during the study period without any major complications. In all, 10 cases of colorectal cancer were diagnosed in 9 patients, of whom 1 died from colorectal cancer. The cumulative incidence of colorectal cancer was 1.4% at 10 years, 2.0% at 20 years, 3.0% at 30 years, and 9.4% at 40 years of disease duration, respectively. The standardized colorectal cancer incidence ratio was 3.01 (95% confidence interval: 1.42-5.91). Major surgery was performed on 65 patients; for 20 of these, the indication for surgery was dysplasia or colorectal cancer. Panproctocolectomy was performed in 43 patients. CONCLUSION: This study supports that colonoscopic surveillance is a safe and effective long-term measure to detect dysplasia and progression to cancer. The low numbers of colorectal cancer-related deaths in our study suggest that early detection of neoplasia and adequate surgical intervention within a surveillance program may reduce colorectal cancer mortality in ulcerative colitis patients.


Assuntos
Colite Ulcerativa/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Estudos de Coortes , Colectomia/métodos , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/cirurgia , Colonoscopia/métodos , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/epidemiologia , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Suécia/epidemiologia
12.
EBioMedicine ; 2(9): 1133-44, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26501111

RESUMO

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.


Assuntos
Dosagem de Genes , Neoplasias da Próstata/genética , Transcriptoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Estudos de Coortes , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Recidiva , Reprodutibilidade dos Testes , Fatores de Risco
13.
Animal ; 8(11): 1777-87, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25046106

RESUMO

Most plant-origin fiber sources used in pig production contains a mixture of soluble and insoluble non-starch polysaccharides (NSP). The knowledge about effects of these sources of NSP on the gut microbiota and its fermentation products is still scarce. The aim of this study was to investigate effects of feeding diets with native sources of NSP on the ileal and fecal microbial composition and the dietary impact on the concentration of short-chain fatty acids (SCFA) and lactic acid. The experiment comprised four diets and four periods in a change-over design with seven post valve t-cecum cannulated growing pigs. The four diets were balanced to be similar in NSP content and included one of four fiber sources, two diets were rich in pectins, through inclusion of chicory forage (CFO) and sugar beet pulp, and two were rich in arabinoxylan, through inclusion of wheat bran (WB) and grass meal. The gut microbial composition was assessed with terminal restriction fragment (TRF) length polymorphism and the abundance of Lactobacillus spp., Enterobacteriaceae, Bacteroides-Prevotella-Porphyromonas and the ß-xylosidase gene, xynB, were assessed with quantitative PCR. The gut microbiota did not cluster based on NSP structure (arabinoxylan or pectin) rather, the effect was to a high degree ingredient specific. In pigs fed diet CFO, three TRFs related to Prevotellaceae together consisted of more than 25% of the fecal microbiota, which is about 3 to 23 times higher (P<0.05) than in pigs fed the other diets. Whereas pigs fed diet WB had about 2 to 22 times higher abundance (P<0.05) of Megasphaera elsdenii in feces and about six times higher abundance (P<0.05) of Lactobacillus reuteri in ileal digesta than pigs fed the other diets. The total amount of digested NSP (r=0.57; P=0.002), xylose (r=0.53; P=0.004) and dietary fiber (r=0.60; P=0.001) in ileal digesta were positively correlated with an increased abundance of Bacteroides-Prevotella-Porphyromonas. The effect on SCFA was correlated to specific neutral sugars where xylose increased the ileal butyric acid proportion, whereas arabinose increased the fecal butyric acid proportion. Moreover, chicory pectin increased the acetic acid proportion in both ileal digesta and feces.


Assuntos
Carboidratos da Dieta/metabolismo , Microbiota/efeitos dos fármacos , Polissacarídeos/metabolismo , Sus scrofa/microbiologia , Sus scrofa/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bacteroides/fisiologia , Dieta/veterinária , Carboidratos da Dieta/administração & dosagem , Ácidos Graxos/metabolismo , Fezes/microbiologia , Fermentação , Conteúdo Gastrointestinal/química , Conteúdo Gastrointestinal/microbiologia , Íleo/química , Íleo/microbiologia , Ácido Láctico/metabolismo , Masculino , Polissacarídeos/administração & dosagem , Porphyromonas/fisiologia , Prevotella/fisiologia , Distribuição Aleatória
14.
Anal Bioanal Chem ; 406(6): 1751-62, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24429974

RESUMO

Anaphylaxis is a potentially life-threatening condition triggered mainly by the release of inflammatory mediators, notably histamine. In pharmaceutical research, drug discovery, and clinical evaluation, it may be necessary to accurately assess the potential of a compound, event, or disorder to promote the release of histamine. In contrast to the measurement of plasma histamine, determination of the stable metabolite 1-methyl-4-imidazoleacetic acid (tele-MIAA) in urine provides a noninvasive and more reliable methodology to monitor histamine release. This study presents a repeatable high-performance liquid chromatography coupled to electrospray mass spectrometry (LC-ESI-MS) method where tele-MIAA is baseline separated from its structural isomer 1-methyl-5-imidazoleacetic acid (pi-MIAA) and an unknown in human urine. The ion-pairing chromatography method, in reversed-phase mode, based on 0.5 mM tridecafluoroheptanoic acid demonstrated high repeatability and was applied in a clinical development program that comprised a large number of clinical samples from different cohorts. The inter- and intra-run precision of the method for tele-MIAA were 8.4 and 4.3%, respectively, at the mean urinary concentration level, while method accuracy was between -16.2 and 8.0% across the linear concentration range of 22-1,111 ng mL(-1). Overall, method precision was greater than that reported in previously published methods and enabled the identification of gender differences that were independent of age or demography. The median concentration measured in female subjects was 3.0 µmol mmol(-1) of creatinine, and for male subjects, it was 2.1 µmol mmol(-1) of creatinine. The results demonstrate that the method provides unprecedented accuracy, precision, and practicality for the measurement of tele-MIAA in large clinical settings.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Histamina/metabolismo , Imidazóis/urina , Espectrometria de Massas por Ionização por Electrospray/métodos , Idoso , Feminino , Humanos , Imidazóis/metabolismo , Limite de Detecção , Masculino , Espectrometria de Massas em Tandem/métodos , Adulto Jovem
15.
Conserv Physiol ; 2(1): cou008, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-27293629

RESUMO

Coastal ecosystems are among the most human-impacted habitats globally, and their management is often critically linked to recovery of declining native species. In the San Francisco Estuary, the Delta Smelt (Hypomesus transpacificus) is an endemic, endangered fish strongly tied to Californian conservation planning. The complex life history of Delta Smelt combined with dynamic seasonal and spatial abiotic conditions result in dissimilar environments experienced among ontogenetic stages, which may yield stage-specific susceptibility to abiotic stressors. Climate change is forecasted to increase San Francisco Estuary water temperature and salinity; therefore, understanding the influences of ontogeny and phenotypic plasticity on tolerance to these critical environmental parameters is particularly important for Delta Smelt and other San Francisco Estuary fishes. We assessed thermal and salinity limits in several ontogenetic stages and acclimation states of Delta Smelt, and paired these data with environmental data to evaluate sensitivity to climate-change stressors. Thermal tolerance decreased among successive stages, with larval fish exhibiting the highest tolerance and post-spawning adults having the lowest. Delta Smelt had limited capacity to increase tolerance through thermal acclimation, and comparisons with field temperature data revealed that juvenile tolerance limits are the closest to current environmental conditions, which may make this stage especially susceptible to future climate warming. Maximal water temperatures observed in situ exceeded tolerance limits of juveniles and adults. Although these temperature events are currently rare, if they increase in frequency as predicted, it could result in habitat loss at these locations despite other favourable conditions for Delta Smelt. In contrast, Delta Smelt tolerated salinities spanning the range of expected environmental conditions for each ontogenetic stage, but salinity did impact survival in juvenile and adult stages in exposures over acute time scales. Our results underscore the importance of considering ontogeny and phenotypic plasticity in assessing the impacts of climate change, particularly for species adapted to spatially and temporally heterogeneous environments.

16.
Spinal Cord ; 51(11): 834-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23999110

RESUMO

STUDY DESIGN: Qualitative method, semi-structured interviews. OBJECTIVES: The aim of the study was to explore the meaning of patient participation in care and rehabilitation from the perspective of patients with spinal cord injury (SCI). SETTING: Post discharge community setting. METHODS: Semi-structured interviews were performed with 10 persons with SCI representing different ages, gender and levels of injury. All interviews were conducted individually and lasted 40-120 min. The interviews were verbally transcribed and the data were analyzed by means of content analysis. RESULTS: All informants stressed the importance of patient participation as a necessary prerequisite for successful care and rehabilitation, but emphasized that participation must be tailored to each patient's own preferences, capacities and needs. They also underscored that the staff should be sensitive and responsive to the fact that desired levels and kinds of participation may vary from patient to patient, as well as for the same patient during the course of the rehabilitation. Five themes reflecting central aspects of participation emerged: respect and integrity, planning and decision-making, information and knowledge, motivation and encouragement, and involvement of family. CONCLUSIONS: Patient participation is a critical component of successful SCI rehabilitation and must be facilitated, promoted and tailored to each patient by the staff. Based on the finding from this study a questionnaire has been developed for assessing patient experiences of five domains of participation in rehabilitation to serve as a tool to help in evaluating provided care and in identifying patients' preferences for participation.


Assuntos
Tomada de Decisões/fisiologia , Participação do Paciente , Traumatismos da Medula Espinal/reabilitação , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Satisfação do Paciente , Inquéritos e Questionários , Adulto Jovem
17.
Spinal Cord ; 51(11): 838-42, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24042990

RESUMO

STUDY DESIGN: A cross-sectional postal questionnaire study. OBJECTIVES: The aim of the study was to evaluate selected psychometric properties of a draft version of the Patient Participation in Rehabilitation Questionnaire (PPRQ) measuring patients' experiences of participation in care and rehabilitation. SETTING: Sweden. METHODS: On the basis of previous qualitative analyses of patient interview data, a 32-item questionnaire covering five domains of participation was developed and sent to 268 persons with spinal cord injury, aged 18-80 years and injured 1-12 years previously. In total, 141 (51%) evaluable questionnaires were returned. Multi-trait analysis was used to assess scaling assumptions by testing item convergent and discriminant validity and internal consistency reliability (Cronbach's α) associated with the hypothesized item-scale structure of the questionnaire. RESULT: Nine items failed to meet scaling assumptions and were omitted. Scaling assumptions were thereafter substantiated for the scales: 'respect and integrity' (6 items); 'planning and decision-making' (4 items); 'information and knowledge' (4 items); 'motivation and encouragement' (5 items); and 'involvement of family' (4 items). Item-scale correlations ranged from 0.67 to 0.85 and most items correlated higher or significantly higher with their hypothesized scale than with other scales. Cronbach's α was 0.89 for all scales. CONCLUSION: The PPRQ appears to adequately assess central aspects of participation in care and rehabilitation from the perspective of patients with spinal cord injury. Further studies using larger samples will be undertaken to confirm the scale structure as well as the sensitivity and responsiveness of the questionnaire.


Assuntos
Participação do Paciente/psicologia , Psicometria , Traumatismos da Medula Espinal/reabilitação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Suécia , Adulto Jovem
18.
Animal ; 7(5): 736-45, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23186946

RESUMO

The impact of fibre level and fibre source on digestibility, gastrointestinal tract (GIT) development, total tract mean retention time (MRT) and growth performance was studied in indigenous Mong Cai (MC) and exotic Landrace × Yorkshire (LY) pigs. The diets were based on maize, rice bran, soyabean meal, fish meal and soyabean oil, and cassava residue (CR) or brewer's grain (BG) as fibrous ingredient sources in the high-fibre diets (HF) and were fed ad libitum. A low-fibre diet (LF), containing around 200 g NDF/kg dry matter (DM), was formulated without CR and BG as feed ingredients. The HF diets (HF-CR and HF-BG) were formulated to contain around 270 g NDF/kg DM. The experiment was arranged as a 2 × 3 factorial completely randomized design with six replications, and lasted 27 days. Increased dietary fibre level resulted in a reduction (P < 0.05) in average daily gain, digestibility of organic matter (OM), CP and gross energy (GE) at the ileum and in the total tract, and in MRT, and an increase (P < 0.05) in the feed conversion ratio and in the weight of the GIT (except for small intestine and caecum). The coefficients of total tract digestibility of fibre fractions were higher in HF diets than in the LF diet, with highest values for diet HF-CR, which had a high proportion of soluble non-starch polysaccharides. MC pigs had longer MRT of digesta than LY pigs (P < 0.05), resulting in higher digestibility at the ileum and in the total tract. Across diets and breeds, the total tract apparent digestibility of OM, CP and GE was positively related (R 2 = 0.80 to 0.84) to the MRT of solids, whereas the MRT was negatively related to the DM intake (R 2 = 0.60).


Assuntos
Ração Animal/análise , Dieta/veterinária , Fibras na Dieta/análise , Fibras na Dieta/farmacologia , Suínos/crescimento & desenvolvimento , Suínos/genética , Fenômenos Fisiológicos da Nutrição Animal , Animais , Digestão/genética , Digestão/fisiologia , Íleo/fisiologia , Vietnã
19.
Animal ; 6(7): 1077-85, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23031467

RESUMO

A total of 30 7-week-old pigs were used to evaluate the effects of chicory inclusion on digestibility, digestive organ size and faecal microbiota. Five diets were formulated: a cereal-based control diet and four diets with inclusion of 80 and 160 g/kg chicory forage (CF80 and CF160), 80 g/kg chicory root (CR80) and a mix of 80 g/kg forage and 80 g/kg chicory root (CFR). Generally, the pigs showed a high growth rate and feed intake, and no differences between the different diets were observed. The coefficients of total tract apparent digestibility (CTTAD) of energy, organic matter and CP did not differ between the control and CF80, whereas they were impaired in diet CF160. The CTTAD of non-starch polysaccharides and especially the uronic acids were higher (P < 0.05) with chicory inclusion, with highest (P < 0.05) values for diet CF160. Coliform counts were lower and lactobacilli : coliform ratio was higher (P < 0.05) in diet CFR than in the control. Global microbial composition was investigated by terminal restriction fragment length polymorphism combined with cloning and sequencing. Analysis of gut microbiota pattern revealed two major clusters where diet CF160 differed from the control and CR80 diet. Chicory forage diets were correlated with an increased relative abundance of one species related to Prevotella and decreased abundance of two other species related to Prevotella. For diet CFR, the relative abundance of Lactobacillus johnsonii was higher than in the other diets. This study shows that both chicory forage and root can be used as fibre sources in pig nutrition and that they modulate the composition of the gut microbiota differently.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Cichorium intybus/química , Suplementos Nutricionais , Digestão/efeitos dos fármacos , Sistema Digestório/crescimento & desenvolvimento , Preparações de Plantas/farmacologia , Sus scrofa/crescimento & desenvolvimento , Animais , Clonagem Molecular , Análise por Conglomerados , Sistema Digestório/microbiologia , Fezes/microbiologia , Metagenoma/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Polimorfismo de Fragmento de Restrição/genética , Análise de Sequência de DNA/veterinária
20.
Animal ; 6(12): 1939-46, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22717208

RESUMO

Most athletic horses are fed a high-starch diet despite the risk of health problems. Replacing starch concentrate with high-energy forage would alleviate these health problems, but could result in a shift in major substrates for muscle energy supply from glucose to short-chain fatty acids (SCFA) due to more hindgut fermentation of fibre. Dietary fat inclusion has previously been shown to promote aerobic energy supply during exercise, but the contribution of SCFA to exercise metabolism has received little attention. This study compared metabolic response with exercise and lactate threshold (VLa4) in horses fed a forage-only diet (F) and a more traditional high-starch, low-energy forage diet (forage-concentrate diet - FC). The hypothesis was that diet F would increase plasma acetate concentration and increase VLa4 compared with diet FC. Six Standardbred geldings in race training were used in a 29-day change-over experiment. Plasma acetate, non-esterified fatty acids (NEFA), lactate, glucose and insulin concentrations and venous pH were measured in samples collected before, during and after a treadmill exercise test (ET, day 25) and muscle glycogen concentrations before and after ET. Plasma acetate concentration was higher before and after exercise in horses on diet F compared with diet FC, and there was a tendency (P = 0.09) for increased VLa4 on diet F. Venous pH and plasma glucose concentrations during exercise were higher in horses on diet F than diet FC, as was plasma NEFA on the day after ET. Plasma insulin and muscle glycogen concentrations were lower for diet F, but glycogen utilisation was similar for the two diets. The results show that a high-energy, forage-only diet alters the metabolic response to exercise and, with the exception of lowered glycogen stores, appears to have positive rather than negative effects on performance traits.


Assuntos
Acetatos/sangue , Glicogênio/metabolismo , Cavalos/metabolismo , Lactatos/sangue , Músculo Esquelético/metabolismo , Silagem/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Análise Química do Sangue/veterinária , Dieta/veterinária , Carboidratos da Dieta/administração & dosagem , Suplementos Nutricionais/análise , Ingestão de Energia , Cavalos/sangue , Cavalos/fisiologia , Masculino , Músculo Esquelético/química , Condicionamento Físico Animal , Amido/administração & dosagem , Suécia
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