RESUMO
1. Metabonomic analysis, via a combination of untargeted and targeted liquid chromatography-mass spectrometry (LC-MS) and untargeted (1)H NMR spectroscopy-based metabolite profiling, was performed on aqueous (AQ) and organic liver extracts from control (SCID) and chimeric humanized (PXB) mice dosed with troglitazone at 0, 300 and 600 mg/kg/day for seven days. 2. LC-MS analysis of AQ liver extracts showed a more "human-like" profile for troglitazone metabolites for PXB, compared with SCID, mice. 3. LC-MS detected differences in endogenous metabolites, particularly lipid species in dosed mice, including elevated triacylglycerols and 1-alkyl,2-acylglycerophosphates as well as lowered diacylglycerophosphocholines and 1-alkyl,2-acylglycerophosphocholines for PXB compared with SCID mouse liver extracts. Following drug administration changes in the relative proportions of the ions for various unsaturated fatty acids were observed for both types of mouse, some of which were specific to PXB or SCID mice. 4. (1)H NMR spectroscopy revealed that AQ PXB mouse liver extracts had elevated amounts of inosine, fumarate, creatine, aspartate, trimethylamine N-oxide, glycerophosphocholine, phosphocholine, choline, glutamine, glutamate, acetate, alanine and lactate relative to SCID mice and decreased histidine, glycogen, α- and ß-glucose, taurine, and glutathione. Increased uracil and tyrosine concentrations were detected for PXB mice on troglitazone administration. 5. Metabonomic profiling thus showed clear differences between humanized and SCID mice, including after administration of troglitazone.
Assuntos
Cromanos/administração & dosagem , Cromanos/metabolismo , Extratos Hepáticos/metabolismo , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/metabolismo , Administração Oral , Animais , Cromanos/farmacocinética , Cromatografia Líquida de Alta Pressão , Humanos , Extratos Hepáticos/análise , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas/métodos , Metabolômica , Camundongos , Camundongos SCID , Camundongos Transgênicos , Tiazolidinedionas/farmacocinética , Quimeras de Transplante , Triglicerídeos/metabolismo , TroglitazonaRESUMO
Background: Satisfactory pain management can have a significant impact on clients' activities of daily living. We questioned what types of pain management education might improve health professional students' knowledge, skills and perceptions? Method: From inception until 30th July 2020, we searched MEDLINE, EBM Reviews, CINAHL Plus, ERIC, EMBASE, Cochrane database and Monash University library. Inclusion criteria were controlled trials of health professional students' pain education compared to alternative education, usual curriculum or no intervention. Studies were limited to English. Data were synthesised using meta-analysis. Results: Fourteen articles were included in this review. For continuous data, meta-analysis demonstrated a clear effect favouring the intervention for knowledge SMD 1.47 [95% CI 1.18, 1.77], skills 0.93 [0.58, 1.28] or perceptions 0.69 [0.31, 1.08]. For dichotomous data, results showed no effect for knowledge 4.21 [0.65, 27.41], skills 2.26 [0.47, 11.01] or perceptions 1.96 [0.66, 5.76]. However, the overall result showed an effect 2.82 [1.20, 6.59] favouring the intervention. Conclusions: In summary, short theoretical interventions are sufficient to change students' knowledge and perceptions. Longer interventions incorporating interactivity improve skills. Further research is required to indicate the best method, outcome measure, length of intervention and follow-up in delivering these pain courses and assessing the cost and long-term retention of information.
RESUMO
Alcoholism is a complex disorder that, in man, appears to be genetically influenced, although the underlying genes and molecular pathways are not completely known. Here, the intragastric alcohol feeding model in rodents was used together with high mass accuracy LC-MS(n) analysis to assess the metabonomic changes in nonpolar metabolite profiles for livers from control and alcohol-treated rats and mice. Ion signals with a peak area variance of less than 30% (based on repeat analysis of a pooled quality control sample analyzed throughout the batch) were submitted to multivariate statistical analysis (using principal components analysis, PCA). PCA revealed robust differences between profiles from control and alcohol-treated animals from both species. The major metabolites seen to differ between control and alcohol-treated animals were identified using high accuracy MS(n) data and verified using external search engines ( http://www.lipidmaps.org ; http://www.hmdb.ca; http://www.genome.jp/kegg/ ) and authentic standards. The main metabolite classes to show major changes in the alcoholic liver-derived samples were fatty acyls, fatty acid ethyl esters, glycerolipids, and phosphatidylethanol homologues. Significant metabolites that were up-regulated by alcohol treatment in both rat and mouse livers included fatty acyls, metabolites such as octadecatrienoic acid and eicosapentaenoic acid, a number of fatty acid ethyl esters such as ethyl arachidonate, ethyl docosahexaenoic acid, ethyl linoleate, and ethyl oleate and phosphatidylethanol (PEth) homologues (predominantly PEth 18:0/18:2 and PEth 16:0/18:2; PEth homologues are currently considered as potential biomarkers for harmful and prolonged alcohol consumption in man). A number of glycerophospholipids resulted in both up-regulation (m/z 903.7436 [M + H](+) corresponding to a triglyceride) and down-regulation (m/z 667.5296 [M + H](+) corresponding to a diglyceride). Metabolite profiles were broadly similar in both mouse and rat models. However, there were a number of significant differences in the alcohol-treated group particularly in the marked down-regulation of retinol and free cholesterol in the mouse compared to the rat. Unique markers for alcohol treatment included ethyl docosahexaenoic acid. Metabolites were identified with high confidence using predominantly negative ion MS(n) data for the fatty acyl components to match to www.lipidmaps.org MS and MS/MS databases; interpreting positive ion data needed to take into account possible adduct ions which may confound the identification of other lipid classes. The observed changes in lipid profiles were consistent with alcohol-induced liver injury in humans.
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Consumo de Bebidas Alcoólicas/metabolismo , Etanol/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metaboloma/efeitos dos fármacos , Animais , Cromatografia Líquida , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/química , Masculino , Espectrometria de Massas , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Ácidos Oleicos/metabolismo , Análise de Componente Principal , Ratos , Ratos WistarRESUMO
BACKGROUND: Scapular dyskinesis has been considered a risk factor for athletic shoulder injury; however, findings in the prospective literature have demonstrated mixed results. PURPOSE: To determine if scapular dyskinesis increases the risk of shoulder injury in athletes. STUDY DESIGN: Meta-analysis. METHODS: A systematic search was conducted on the MEDLINE, CINAHL Plus, SPORTDiscus, and Embase databases to identify prospective studies examining scapular dyskinesis and shoulder injury risk in athletes. Studies were included if they assessed participants using a dynamic scapular assessment at baseline and monitored for the development of shoulder injury. Data from the studies were subject to meta-analysis using the Mantel-Haenszel method to produce a pooled risk ratio. RESULTS: Seven studies were eligible for inclusion, resulting in 212 shoulder injuries observed across 923 athletes. Scapular dyskinesis was present in 46% of participants, and these athletes had an injury rate of 25%. The presence of scapular dyskinesis displayed a trend to increase the risk of shoulder injury, but this was not statistically significant (risk ratio, 1.07; 95% CI, 0.85-1.34; P = .59). CONCLUSION: Scapular dyskinesis was not significantly associated with the development of shoulder injury in athletes. REGISTRATION: CRD42019133089 (PROSPERO).
Assuntos
Discinesias , Lesões do Ombro , Articulação do Ombro , Atletas , Fenômenos Biomecânicos , Discinesias/epidemiologia , Discinesias/etiologia , Humanos , Estudos Prospectivos , Fatores de Risco , EscápulaRESUMO
BACKGROUND: Rotator cuff-related shoulder pain (RCRSP) is a common and disabling musculoskeletal condition. Internet-based and telerehabilitation delivery of recommended care may improve access to care and improve adherence and outcomes. OBJECTIVE: The primary aim of this pilot randomized controlled trial was to assess the feasibility of a 12-week internet-delivered intervention for RCRSP comparing advice only, recommended care, and recommended care with group-based telerehabilitation. METHODS: Reporting was in accordance with the Consolidated Standards of Reporting Trials (CONSORT) checklist for pilot and feasibility trials. People with a primary complaint of RCRSP for 3 months or longer were identified via a paid Facebook strategy. Screening involved an online questionnaire followed by a 20-minute telehealth assessment. Participants were randomly allocated (via a Zelen design) to receive (1) advice only, (2) recommended care (internet-delivered evidence-based exercise and education), or (3) recommended care and telerehabilitation (including a weekly group teleconference session). Progression criteria for a full-scale trial included (1) recruitment of 20% or greater of eligible participants, (2) acceptable adherence (two or more of the three prescribed weekly sessions) among 70% or greater of participants, (3) 80% or greater retention of participants, (4) absence of intervention-related serious adverse events, and (5) 80% or greater response rates to questionnaires. Secondary clinical and patient knowledge outcomes were collected (via email or text) at baseline, six weeks, and 12 weeks (for clinical and patient knowledge), and within-group change was reported descriptively. RESULTS: We enrolled 36 of 38 (95%) eligible participants and all participants were recruited within a 3-week period. Of the 36 participants, 12 participants were allocated to each of the three trial arms. The mean age of participants was between 51 and 56 years, and 83% (10/12) to 92% (11/12) were female. Retention at the 12-week endpoint was 94% (34/36) and response to email questionnaires at other time points was 83% or greater. We found acceptable adherence (defined as greater than 70% of participants performing exercise 2 or 3 times/week) in the recommended care group with telerehabilitation but not in the recommended care group without telerehabilitation. There was a total of 24 adverse events over 108 person-months of observation. All adverse events were mild or moderate (mainly muscle and shoulder symptoms), with the exception of one instance of elective surgery (unrelated to the person's shoulder condition). CONCLUSIONS: Our prespecified success criteria were met or exceeded, but there was a gender imbalance toward women. It is feasible to progress to a fully powered trial, but strategies to address the gender imbalance need to be implemented. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12620000248965); https://tinyurl.com/yy6eztf5.