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1.
Clin Radiol ; 78(5): e368-e376, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36863883

RESUMO

AIM: To evaluate primary and secondary pathologies of interest using an artificial intelligence (AI) platform, AI-Rad Companion, on low-dose computed tomography (CT) series from integrated positron-emission tomography (PET)/CT to detect CT findings that might be overlooked. MATERIALS AND METHODS: One hundred and eighty-nine sequential patients who had undergone PET/CT were included. Images were evaluated using an ensemble of convolutional neural networks (AI-Rad Companion, Siemens Healthineers, Erlangen, Germany). The primary outcome was detection of pulmonary nodules for which the accuracy, identity, and intra-rater reliability was calculated. For secondary outcomes (binary detection of coronary artery calcium, aortic ectasia, vertebral height loss), accuracy and diagnostic performance were calculated. RESULTS: The overall per-nodule accuracy for detection of lung nodules was 0.847. The overall sensitivity and specificity for detection of lung nodules was 0.915 and 0.781. The overall per-patient accuracy for AI detection of coronary artery calcium, aortic ectasia, and vertebral height loss was 0.979, 0.966, and 0.840, respectively. The sensitivity and specificity for coronary artery calcium was 0.989 and 0.969. The sensitivity and specificity for aortic ectasia was 0.806 and 1. CONCLUSION: The neural network ensemble accurately assessed the number of pulmonary nodules and presence of coronary artery calcium and aortic ectasia on low-dose CT series of PET/CT. The neural network was highly specific for the diagnosis of vertebral height loss, but not sensitive. The use of the AI ensemble can help radiologists and nuclear medicine physicians to catch CT findings that might be overlooked.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Inteligência Artificial , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Cálcio , Reprodutibilidade dos Testes , Dilatação Patológica , Achados Incidentais , Nódulos Pulmonares Múltiplos/patologia , Redes Neurais de Computação , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia
2.
BMC Public Health ; 22(1): 276, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-35144592

RESUMO

BACKGROUND: An extended version of the theory of planned behaviour (TPB) was used to inform the design of a framework for an educational resource around e-cigarette use in young people. METHODS: A sequential exploratory design was employed. In Phase 1, elicited behavioural, normative and control beliefs, via 7 focus groups with 51 participants, aged 11-16 years, identified salient beliefs around e-cigarette use. These were used to construct a questionnaire administered to 1511 young people aged 11-16 years, which determined predictors of e-cigarette use and ever use. In Phase 2, sociodemographic variables, e-cigarette knowledge, access, use, marketing and purchasing of e-cigarettes and smoking behaviour were also gathered. The composite findings from Phase 1 and 2 informed the design of a post primary educational resource in Phase 3 around e-cigarette use. RESULTS: Current e-cigarette use was 4%, with almost 23% reporting ever use, suggesting current use is stable but experimentation may be increasing in this cohort. Sociodemographic variables, knowledge of e-cigarettes, smoking behaviour and TPB variables (direct and indirect measures of attitudes, subjective norm, and perceived behavioural control) accounted for 17% of the variance in current e-cigarette use, with higher intentions to use e-cigarettes within the next month, having the strongest impact on use (p < 0.001), followed by self-efficacy (p = 0.016). Sociodemographic and TPB variables accounted for 65% of the variance in intentions to use e-cigarettes in the next month; current e-cigarette use (p < 0.001), more positive attitudes (p < 0.001), stronger social influence (p < 0.001), higher self-efficacy (p < 0.001), higher control beliefs (p < 0.001) and greater motivation to use e-cigarettes (p < 0.001) were the main predictors of intentions. Phases 1 and 2 informed the mapping of key predictors of intentions and use of e-cigarettes onto the Theoretical Domains Framework, which identified appropriate intervention functions and behaviour change techniques. CONCLUSIONS: This paper is the first to bridge the theoretical-practice gap in an area of significant public health importance through the development of a framework for a novel theory driven school-based educational resource aimed at reducing experimentation and uptake of e-cigarette use in young people.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Adolescente , Escolaridade , Humanos , Intenção , Motivação , Instituições Acadêmicas
3.
J Appl Microbiol ; 130(2): 356-369, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32681565

RESUMO

AIMS: To investigate the microbiological and nutritional quality of liquid finisher pig feed on commercial production units and the factors influencing this. METHODS AND RESULTS: Microbiological and physio-chemical analyses were performed on liquid feed sampled from the mixing tank and troughs of the finisher section of eight commercial pig units. Lactic acid bacteria, yeast and Escherichia coli counts, as well as lactic acid, ethanol and acetate concentrations were higher in residual feed sampled from the troughs compared with mixing tank samples (P < 0·001). Feed pH, as well as lysine, methionine and threonine concentrations and gross energy were all lower in the residual trough samples (P < 0·001). Liquid co-products reduced E. coli counts in the residual trough samples (P < 0·05), pH in the mixing tank (P < 0·01) and fresh trough samples (P < 0·05) and mould counts at all three sampling locations (P < 0·01) but sanitation practices had no impact. CONCLUSIONS: Even when considered unfermented, a considerable degree of spontaneous fermentation occurs in liquid feed, with resultant negative effects on nutritional quality. SIGNIFICANCE AND IMPACT OF THE STUDY: This is one of the first studies showing that uncontrolled fermentation of fresh liquid pig feed is commonplace on commercial units, highlighting the need for implementation of suitable control strategies.


Assuntos
Ração Animal/microbiologia , Microbiologia de Alimentos , Ração Animal/análise , Animais , Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Fermentação , Fungos/isolamento & purificação , Fungos/metabolismo , Concentração de Íons de Hidrogênio , Lactobacillales/isolamento & purificação , Lactobacillales/metabolismo , Suínos , Leveduras/isolamento & purificação , Leveduras/metabolismo
4.
Br J Nutr ; 123(3): 255-263, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31640819

RESUMO

The identification of natural bioactive compounds which can prevent the post-weaning growth check and enhance gastrointestinal health in the absence of in-feed medications is an urgent priority for the swine industry. The objective of this experiment was to determine the effects of increasing dietary inclusion levels of laminarin in the first 14 d post-weaning on pig growth performance and weaning associated intestinal dysfunction. At weaning, ninety-six pigs (8·4 (sd 1·09) kg) (meatline boars × (large white × landrace sows)) were blocked by live weight, litter and sex and randomly assigned to: (1) basal diet; (2) basal + 100 parts per million (ppm) laminarin; (3) basal + 200 ppm laminarin and (4) basal + 300 ppm laminarin (three pigs/pen). The appropriate quantity of a laminarin-rich extract (65 % laminarin) was added to the basal diet to achieve the above dietary inclusion levels of laminarin. After 14 d of supplementation, eight pigs from the basal group and the best-performing laminarin group were euthanised for sample collection. The 300 ppm laminarin group was selected as this group had higher ADFI compared with all other groups and higher ADG than the basal group (P < 0·05). Laminarin supplementation increased villus height in the duodenum and jejunum (P < 0·05). Laminarin supplementation increased the expression of SLC2A8/GLUT8 in the duodenum, SLC2A2/GLUT2, SLC2A7/GLUT7, SLC15A1/PEPT1 and FABP2 in the jejunum and SLC16A1/MCT1 in the colon. Laminarin supplementation reduced Enterobacteriaceae numbers in the caecum (P < 0·05) and increased lactobacilli numbers (P < 0·05), total volatile fatty acid concentrations and the molar proportions of butyrate (P < 0·01) in the colon. In conclusion, 300 ppm laminarin from a laminarin-rich extract has potential, as a dietary supplement, to improve performance and prevent post-weaning intestinal dysfunction.


Assuntos
Suplementos Nutricionais , Glucanos , Enteropatias/prevenção & controle , Extratos Vegetais/administração & dosagem , Desmame , Ração Animal/análise , Animais , Colo/metabolismo , Dieta/veterinária , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Expressão Gênica , Enteropatias/etiologia , Mucosa Intestinal/metabolismo , Intestino Grosso/microbiologia , Intestino Delgado/crescimento & desenvolvimento , Masculino , Suínos
5.
Br J Nutr ; : 1-36, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32127055

RESUMO

Genetic selection for increased sow prolificacy has resulted in decreased mean piglet birth-weight. This study aimed to investigate the effect of L-carnitine (CAR) supplementation to sows during gestation and/or lactation on sow productivity, semitendinosus muscle (STM) maturity, and lifetime growth in progeny. Sixty-four sows were randomly assigned to one of four dietary treatments at breeding until weaning; CONTROL (0mg CAR/d), GEST (125mg CAR/d during gestation), LACT (250mg CAR/d during lactation), and BOTH (125mg CAR/d during gestation & 250mg CAR/d during lactation). The total number of piglets born per litter was greater for sows supplemented with CAR during gestation (17.3 v 15.8 ± 0.52; P<0.05). Piglet birth-weight (total and live) was unaffected by sow treatment (P>0.05). Total myofibre number (P=0.08) and the expression level of selected myosin heavy chain genes in the STM (P<0.05) was greater in piglets of sows supplemented with CAR during gestation. Pigs from sows supplemented with CAR during gestation had lighter carcasses at slaughter than pigs from non-supplemented sows during gestation (83.8 v 86.7 ± 0.86kg; P<0.05). In conclusion, CAR supplementation during gestation increased litter size at birth without compromising piglet birth-weight. Results also showed that the STM of piglets born to sows supplemented with CAR during gestation was more developed at birth. However, carcass weight at slaughter was reduced in progeny of sows supplemented with CAR during gestation. The CAR supplementation strategy applied during gestation in this study could be utilized by commercial pork producers to increase sow litter size and improve offspring muscle development.

6.
Ann Oncol ; 30(2): 310-316, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30566587

RESUMO

BACKGROUND: Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited. PATIENTS AND METHODS: We pooled individual-level data from seven cohort and five case-control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect. RESULTS: At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76-0.98] and 0.86 [95% CI 0.76-0.97], respectively, for aspirin; 0.87 [95% CI 0.76-1.00] and 0.84 [0.74-0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2-6 times/week (OR = 0.81, 95% CI 0.68-0.96) than for daily use (0.91, 0.80-1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen. CONCLUSION: Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Neoplasias do Endométrio/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias do Endométrio/induzido quimicamente , Feminino , Seguimentos , Humanos , Prognóstico , Fatores de Risco , Estados Unidos/epidemiologia
7.
J Anim Physiol Anim Nutr (Berl) ; 102(3): 799-809, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29359525

RESUMO

This study investigates the effect of dietary supplementation of a ß-glucanase and ß-xylanase enzyme mix to barley based diets, at two different chemical compositions achieved through different agronomical conditions on growth performance, coefficient of apparent total tract digestibility (CATTD) of nutrients, selected faecal microbial populations and faecal scores in piglets. Sixty-four piglets (11.7 kg (SD 0.96)) housed in pens of two were assigned to one of four dietary treatments (n = 8). The dietary treatments were as follows: (T1) low quality barley diet, (T2) low quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement, (T3) high quality barley diet and (T4) high quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement. Piglets offered the low quality barley-based diet had a higher (p < .05) average daily gain (ADG) (0.73 vs. 0.69 kg, SEM 0.001), gain:feed (G:F) ratio (0.61 vs. 0.58 kg, SEM 0.011) and a higher CATTD (p < .001) of dry matter (DM), organic matter (OM), nitrogen (N), ash, gross energy (GE) and neutral detergent fibre (NDF) compared with piglets offered the high quality barley diet. Piglets offered the high quality barley-based diet had reduced faecal scores compared to piglets offered the low quality barley-based diet (2.44 vs. 2.57, SEM 0.036) (p < .05). There was a higher population of Lactobacillus spp. (11.6 vs. 10.5 log gene copy number/g faeces, SEM 0.177) (p < .001) and total volatile fatty acid (VFA) concentration (185 vs. 165 mmol/g faeces, SEM 5.658) (p < .001) in the faeces of piglets offered the high quality barley-based diet compared to piglets offered the low quality barley-based diet. The inclusion of a ß-glucanase and ß-xylanase enzyme complex had no effect on any variable measured. In conclusion, the higher quality barley-based diet showed beneficial effects on the faecal Lactobacillus spp. population and faecal scores of the piglets; however, the higher level of ß-glucans in the diet decreased nutrient digestibility and subsequently decreased the performance.


Assuntos
Ração Animal/análise , Dieta/veterinária , Suplementos Nutricionais , Hordeum/química , Suínos/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , DNA Bacteriano/genética , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Fezes/química , Fezes/microbiologia , Feminino , Masculino
8.
Ir Med J ; 111(1): 674, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29869855

RESUMO

This study evaluated the prevention of bone fragility fractures in a representative sample of four Irish general practices. The clinical records of 243 patients potentially at risk of bone fragility were studied. One hundred and fourteen (47%) had a dual energy x-ray absorptiometry (DEXA) scan. Osteoporosis was established in 42 (17%) and osteopaenia in 28 (11%). One hundred and fifty-two (63%) were currently being prescribed bisphosphonates. Thirty-four (22%) of those on bisphosphonates did not have a baseline DEXA scan performed prior to commencing treatment and further analysis did not show a clear rationale for initiation of the treatment in this group of patients. Forty-six (30%) patients on bisphosphonates had been prescribed them for over 5 years without any apparent review to see if they were still indicated. There was no record of any of the practices having carried out a fracture risk score assessment prior to commencing bone fragility treatment. The implications are that bone fragility management warrants urgent review.


Assuntos
Absorciometria de Fóton/estatística & dados numéricos , Fraturas por Osteoporose/prevenção & controle , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Medicina Geral/estatística & dados numéricos , Humanos , Irlanda/epidemiologia , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/diagnóstico por imagem , Atenção Primária à Saúde
9.
Pharmacogenomics J ; 17(5): 452-460, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27573236

RESUMO

The Hedgehog pathway is one of the major driver pathways in pancreatic ductal adenocarcinoma. This study investigated prognostic importance of Hedgehog signaling pathway in pancreatic cancer patients who underwent a radical resection. Tumors and adjacent non-neoplastic pancreatic tissues were obtained from 45 patients with histologically verified pancreatic cancer. The effect of experimental taxane chemotherapy on the expression of Hedgehog pathway was evaluated in vivo using a mouse xenograft model prepared using pancreatic cancer cell line Paca-44. Mice were treated by experimental Stony Brook Taxane SB-T-1216. The transcript profile of 34 Hedgehog pathway genes in patients and xenografts was assessed using quantitative PCR. The Hedgehog pathway was strongly overexpressed in pancreatic tumors and upregulation of SHH, IHH, HHAT and PTCH1 was associated with a trend toward decreased patient survival. No association of Hedgehog pathway expression with KRAS mutation status was found in tumors. Sonic hedgehog ligand was overexpressed, but all other downstream genes were downregulated by SB-T-1216 treatment in vivo. Suppression of HH pathway expression in vivo by taxane-based chemotherapy suggests a new mechanism of action for treatment of this aggressive tumor.


Assuntos
Carcinoma Ductal Pancreático/tratamento farmacológico , Proteínas Hedgehog/genética , Neoplasias Pancreáticas/tratamento farmacológico , Taxoides/uso terapêutico , Transcriptoma/efeitos dos fármacos , Idoso , Animais , Carcinoma Ductal Pancreático/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Mutação , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Taxoides/administração & dosagem , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Transfus Med ; 27(2): 122-131, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28144996

RESUMO

OBJECTIVE: Retrospective audit of IVIG Request Forms in four Ontario tertiary care centres: to determine the case mix of new IVIG requests, to authenticate information provided, and to determine documentation of clinical efficacy. AIMS: To understand contributors to increases in IVIG utilisation and to determine whether IVIG is being used and monitored appropriately. INTRODUCTION: Intravenous immunoglobulin (IVIG) use in Canada is high compared with other developed countries. We performed a retrospective audit of new IVIG Request Forms across four tertiary care centres in Ontario, one with an active surveillance programme, to determine the case mix, authenticate information provided and assess documentation of efficacy. METHODS: Consecutive adult patients with a first-time IVIG request in 2014 were included. The ordering physician specialty, form completeness, documentation of diagnostic criteria for the medical condition and indication for IVIG use and documentation of efficacy were assessed by form and chart review. RESULTS: Of 178 patients, the most common indications for IVIG were immune thrombocytopenia (24.2%) and secondary immune deficiency (20.2%). The most frequent prescribers were haematologists (37.6%) and neurologists (10.7%). Other conditions not listed on the form represented 24.2% of cases, with most not indicated in current guidelines. A total of 32.6% of cases overall lacked verification of diagnostic criteria and 51.7% lacked verification for IVIG utilisation criteria, with the number of cases meeting criteria based on documentation being higher at the active surveillance site (P = 0.005). A total of 19.1% of cases had a discrepancy between the indication written on the form and the documented clinical diagnosis. A total of 18.7% of clinic notes following IVIG had no mention of efficacy. CONCLUSION: Our audit demonstrates a lack of compliance with IVIG Request Form requirements, a lack of documentation of diagnostic criteria and efficacy, and suggests inappropriate use of IVIG. Current implementation of the form may not be sufficient as a strategy for improving appropriate IVIG use.


Assuntos
Imunoglobulinas Intravenosas , Auditoria Médica , Prontuários Médicos , Centros de Atenção Terciária , Adulto , Feminino , Humanos , Masculino , Ontário , Estudos Retrospectivos
11.
J Anim Physiol Anim Nutr (Berl) ; 101(6): 1273-1285, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27859742

RESUMO

Three experiments were conducted to investigate the interaction between zinc methionine (ZnM) and laminarin (LAM) on piglet growth performance and intestinal health post-weaning. Experiment 1 was designed as 2 × 2 factorial with four treatments [n = 8, weaning age (WA) 24 days, live weight (LW) 7.15 kg]: (i) basal diet (BD); (ii) BD + 500 mg/kg ZnM; (iii) BD + 300 mg/kg LAM; and (iv) BD + 500 mg/kg ZnM + 300 mg/kg LAM. There was an interaction (p < 0.05) between LAM and ZnM. Pigs that were offered the LAM diet had a similar performance to the BD. However, when combining LAM with ZnM, pigs had reduced average daily gain (ADG), gain-to-feed ratio (G:F) and LW at slaughter at day 8 post-weaning compared to the ZnM. Both LAM and ZnM improved the small intestinal morphology of the pigs at day 8 post-weaning. Experiment 2 was designed as 2 × 2 factorial with four dietary treatments (n = 9, WA 24 days, LW 7.32 kg): (i) BD; (ii) BD + 500 mg/kg ZnM; (iii) BD + 175 mg/kg LAM; and (iv) BD + 500 mg/kg ZnM + 175 mg/kg LAM. The ADG and average daily feed intake were improved between day 0 and 31 PW when pigs were offered a LAM diet (p < 0.01). Faecal scores were reduced between day 0 and day 31 post-weaning with ZnM (p < 0.001). Experiment 3 consisted of four dietary treatments (n = 10, WA 24 days, LW 7.32 kg): (i) BD; (ii) BD + 3300 mg/kg zinc oxide (ZnO); (iii) BD + 500 mg/kg ZnM; and (iv) BD + 175 mg/kg LAM. Pigs that were offered the ZnO diet had an increased ADG compared to the BD or ZnM diets (p < 0.01). Pigs that were offered the LAM diet had increased ADG compared to the ZnM diet (p < 0.05). Faecal scores were reduced between day 0 and day 31 PW with ZnM or ZnO supplementation (p < 0.001). In conclusion, the inclusion of 175 mg/kg LAM and ZnO improved ADG while both ZnO and ZnM reduced the faecal scores post-weaning.


Assuntos
Diarreia/veterinária , Glucanos/farmacologia , Intestino Delgado/efeitos dos fármacos , Metionina/análogos & derivados , Compostos Organometálicos/farmacologia , Ração Animal/análise , Animais , Diarreia/prevenção & controle , Dieta/veterinária , Suplementos Nutricionais , Enteropatias/prevenção & controle , Metionina/farmacologia , Suínos , Doenças dos Suínos/prevenção & controle
12.
Ir Med J ; 110(5): 563, 2017 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-28737304

RESUMO

Several commonly completed tests have low diagnostic yield in the setting of transient loss of consciousness (T-LOC). We estimated the use and cost of inappropriate investigations in patients admitted with T-LOC and assessed if these patients were given a definitive diagnosis for their presentation. We identified 80 consecutive patients admitted with T-LOC to a university teaching hospital. Eighty-eight percent (70/80) had a computerized topography (CT) brain scan and 49% (34/70) of these scans were inappropriate based on standard guidelines. Almost half (17/80) of electroencephalograms (EEG) and 82% (9/11) of carotid doppler ultrasound performed were not based on clinical evidence of seizure or stroke respectively. Forty-four percent (35/80) of patients had no formal diagnosis documented for their presentation. Inappropriate investigation in T-LOC is very prevalent in the acute hospital, increasing cost of patient care. In addition, there is poor diagnostic formulation for T-LOC making recurrent events more likely in the absence of definitive diagnoses.


Assuntos
Eletroencefalografia/estatística & dados numéricos , Hospitalização , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Inconsciência/etiologia , Mau Uso de Serviços de Saúde/estatística & dados numéricos , Humanos , Prevalência , Convulsões/diagnóstico por imagem , Inconsciência/diagnóstico por imagem
14.
Ann Oncol ; 27(9): 1712-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27287210

RESUMO

BACKGROUND: ARCHER 1042, a randomized phase II trial, explored the impact of prophylactic treatment on select dermatologic adverse events of interest (SDAEI), diarrhea, and mucositis associated with dacomitinib, an oral irreversible pan-human epidermal growth factor receptor (HER) inhibitor, in development for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC treated with dacomitinib were enrolled in two cohorts. Cohort I patients were randomized 1:1 to receive oral doxycycline or placebo (4 weeks). Cohort II patients received oral VSL#3 probiotic plus topical alclometasone. Primary end points for Cohorts I and II were incidence of all grade and grade ≥2 SDAEI in the first 8 weeks of treatment and quality of life (QoL) assessed by the Skindex-16 survey. Additional primary end points for Cohort II were incidence of all grade and grade ≥2 diarrhea and mucositis in the first 8 weeks of treatment; QoL regarding diarrhea and mucositis incidence was assessed by the modified-Oral Mucositis Daily Questionnaire. RESULTS: Cohort I randomized 114 evaluable patients: 56 in the doxycycline arm, 58 in the placebo arm. Cohort II enrolled 59 evaluable patients. Doxycycline significantly reduced the incidence of grade ≥2 SDAEI by 50% (P = 0.016) compared with placebo. The incidence of all grade SDAEI was lower with doxycycline than with placebo but did not reach statistical significance. Doxycycline was associated with less deterioration in QoL compared with placebo. Alclometasone was associated with less deterioration in QoL compared with placebo but did not statistically significantly reduce the incidence of all grade or grade ≥2 SDAEI. VSL#3 did not reduce the incidence of all grade or grade ≥2 diarrhea and did not impact mucositis scores. CONCLUSIONS: Doxycycline was effective as a prophylactic treatment for dacomitinib-induced grade ≥2 SDAEI. Both doxycycline and alclometasone reduced the negative impact in patient-reported dermatologic AEs. The probiotic was not effective for preventing diarrhea or mucositis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gastroenteropatias/patologia , Quinazolinonas/administração & dosagem , Dermatopatias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Qualidade de Vida , Quinazolinonas/efeitos adversos , Dermatopatias/induzido quimicamente , Resultado do Tratamento
15.
Clin Exp Immunol ; 186(2): 266-276, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27406528

RESUMO

The technique of challenging postmortem tissue explants with inflammation inducer such as lipopolysaccharide (LPS) followed by gene expression analysis is used widely for evaluating the immune-suppressing effect of bioactives. Using porcine colonic tissue as an ex-vivo model of mammalian intestinal gut, this study evaluated the effect of incubation time on the integrity of gene transcripts and activation of inflammatory immune gene cascade by LPS treatment. Post-slaughter colon was removed surgically and explants were incubated for 0, 3, 6 and 12 h and the abundance of mRNA transcripts of a panel of 92 immune genes were evaluated using quantitative polymerase chain reaction (qPCR) arrays. The mRNA transcripts were highly intact after 0 and 3 h of incubation; however, after 6 h the degradation was clearly evident. Following 3 h incubation, 98·8% and 100% mRNA transcripts were detectable in the colonic tissue harvested from weaned and mature pigs, respectively. In the explants of weaned piglets, LPS treatment activated inflammatory signalling pathways [high mobility group B1 (HMGB1), dendritic cell maturation, interleukin (IL)-6, IL-8, IL-17F], while these pathways were inhibited by dexamethasone treatment. Activations of inflammatory genes were also evident in the explants collected from the mature pigs subjected to ex-vivo incubation for 3 h in the absence or presence of LPS. It is concluded that the colonic explant remains physiologically viable and responsive to immunological challenge for up to 3 h ex-vivo.


Assuntos
Colo/imunologia , Colo/metabolismo , Regulação da Expressão Gênica , Imunidade/genética , Inflamação/genética , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Animais , Anti-Inflamatórios/farmacologia , Biomarcadores , Colo/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Inflamação/patologia , Masculino , Transdução de Sinais/efeitos dos fármacos , Suínos
16.
Faraday Discuss ; 187: 273-98, 2016 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-27063935

RESUMO

Studies of drug-cell interactions in cancer model systems are essential in the preclinical stage of rational drug design, which relies on a thorough understanding of the mechanisms underlying cytotoxic activity and biological effects, at a molecular level. This study aimed at applying complementary vibrational spectroscopy methods to evaluate the cellular impact of two Pt(ii) and Pd(ii) dinuclear chelates with spermine (Pt2Spm and Pd2Spm), using cisplatin (cis-Pt(NH3)2Cl2) as a reference compound. Their effects on cellular metabolism were monitored in a human triple-negative metastatic breast cancer cell line (MDA-MB-231) by Raman and synchrotron-radiation infrared microspectroscopies, for different drug concentrations (2-8 µM) at 48 h exposure. Multivariate data analysis was applied (unsupervised PCA), unveiling drug- and concentration-dependent effects: apart from discrimination between control and drug-treated cells, a clear separation was obtained for the different agents studied - mononuclear vs. polynuclear, and Pt(ii) vs. Pd(ii). Spectral biomarkers of drug action were identified, as well as the cellular response to the chemotherapeutic insult. The main effect of the tested compounds was found to be on DNA, lipids and proteins, the Pd(ii) agent having a more significant impact on proteins while its Pt(ii) homologue affected the cellular lipid content at lower concentrations, which suggests the occurrence of distinct and unconventional pathways of cytotoxicity for these dinuclear polyamine complexes. Raman and FTIR microspectroscopies were confirmed as powerful non-invasive techniques to obtain unique spectral signatures of the biochemical impact and physiological reaction of cells to anticancer agents.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Espectrofotometria Infravermelho , Análise Espectral Raman , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Humanos , Espermina/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Vibração
17.
Appl Opt ; 55(32): 9054-9059, 2016 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-27857289

RESUMO

In this paper, we examine a laser-based approach to remotely initiate, measure, and differentiate acoustic and vibrational emissions from trace quantities of explosive materials against their environment. Using a pulsed ultraviolet laser (266 nm), we induce a significant (>100 Pa) photoacoustic response from small quantities of military-grade explosives. The photoacoustic signal, with frequencies predominantly between 100 and 500 kHz, is detected remotely via a wideband laser Doppler vibrometer. This two-laser system can be used to rapidly detect and discriminate explosives from ordinary background materials, which have significantly weaker photoacoustic response. A 100 ng/cm2 limit of detection is estimated. Photoablation is proposed as the dominant mechanism for the large photoacoustic signals generated by explosives.

18.
Br J Cancer ; 113(5): 817-26, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26151456

RESUMO

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Obesidade/patologia , Neoplasias Ovarianas/patologia , Índice de Massa Corporal , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Epiteliais e Glandulares/mortalidade , Obesidade/mortalidade , Neoplasias Ovarianas/mortalidade
19.
Br J Nutr ; 112(12): 1955-65, 2014 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-25345748

RESUMO

In the present study, a 2 × 2 factorial arrangement was conducted to investigate the effect of maternal supplementation with seaweed extracts ( - SWE v. +SWE, n 20) from day 83 of gestation until weaning (day 28) on post-weaning (PW) growth performance, faecal score, faecal enterotoxigenic Escherichia coli (ETEC) toxin quantification, intestinal histology and cytokine mRNA of unchallenged and ETEC-challenged pigs. Pigs were ETEC challenged on day 9 PW. There was a maternal treatment × challenge (SWE × ETEC) interaction effect on growth performance and faecal score (P< 0.05). Pigs from SWE-supplemented sows and ETEC-challenged (SE) had higher average daily gain (ADG) during 0-13 d PW and reduced faecal score during 0-72 h post-challenge than those from basal-fed sows and ETEC-challenged (BE) (P< 0.05). However, there was no difference between unchallenged pigs from the SWE-supplemented sows (SC) and basal-fed sows (BC) (P>0.10). Pigs from the SWE-supplemented sows had reduced heat-labile enterotoxin gene copy numbers than those from the basal-fed sows (P< 0.05). Maternal SWE supplementation increased the villus height in the ileum of pigs (P< 0.05). There was a SWE × ETEC interaction effect (P< 0.05) on IL-6 mRNA and a SWE × gastrointestinal (GI) region interaction effect (P< 0.05) on transforming growth factor-ß1 (TGF-ß1) and TNF-α mRNA. IL-6 mRNA was down-regulated in SC pigs than BC pigs (P< 0.05). However, there was no difference in IL-6 mRNA between SE and BE pigs. The mRNA of TGF-ß1 and TNF-α was down-regulated in the colon of pigs from the SWE-supplemented sows compared with those from the basal-fed sows (P< 0.05). However, there was no difference in TGF-ß1 and TNF-α mRNA in the ileum between the pigs from the SWE-supplemented sows and basal-fed sows. In conclusion, maternal SWE supplementation improves ADG and the aspects of GI health of weaned pigs following an ETEC challenge.


Assuntos
Citocinas/metabolismo , Suplementos Nutricionais , Enterotoxinas/imunologia , Escherichia coli , Intestinos/efeitos dos fármacos , Alga Marinha , Aumento de Peso/efeitos dos fármacos , Animais , Colo/metabolismo , Citocinas/genética , Regulação para Baixo , Enterotoxinas/genética , Fezes , Feminino , Íleo/crescimento & desenvolvimento , Íleo/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/crescimento & desenvolvimento , Intestinos/microbiologia , Laminaria , Extratos Vegetais/farmacologia , Gravidez , RNA Mensageiro/metabolismo , Suínos , Desmame
20.
Br J Nutr ; 111(5): 798-807, 2014 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-24131869

RESUMO

Seaweed extracts (SWE) rich in laminarin and fucoidan have shown promise as a supplement for weaned piglets. However, successful application in pig nutrition depends on their bioactivity in the presence of additives such as ZnO. In the present study, a 2 × 2 factorial experiment was carried out to investigate the effect of the interaction between SWE and ZnO on the growth performance, digestibility and faecal characteristics of 192 weaned piglets (6·5 kg). The piglets were penned in groups of 4 (n 12 pens). The study consisted of two phases after weaning: a starter diet period from the day of weaning (0 d) to 21 d and a transition diet period from 21 to 40 d. The dietary treatments were as follows: (1) control diet; (2) control diet+ZnO; (3) control diet+SWE; (4) control diet+ZnO+SWE. Diets containing ZnO improved the faecal consistency of the piglets throughout the experimental period (0-40 d). An effect of the interaction between ZnO and SWE on several variable was observed. The diet containing only SWE or ZnO improved the feed conversion efficiency of the piglets during the transition diet period; however, this effect was not observed when the diet containing both ZnO and SWE was fed. The diet containing only SWE increased the N and organic matter digestibility of the piglets; however, this effect was not observed in the presence of ZnO. An interaction between ZnO and SWE was observed, whereby the faecal counts of Escherichia coli were decreased when piglets were fed the diet containing only SWE, but not when fed the diet containing both SWE and ZnO. In summary, SWE and ZnO improve growth performance when given alone, but not when given in combination. The biological effect of SWE on selected digestibility and faecal characteristics was markedly different when compared with that of ZnO.


Assuntos
Produtos Biológicos/uso terapêutico , Dieta/veterinária , Trato Gastrointestinal/metabolismo , Laminaria/química , Alga Marinha/química , Sus scrofa/crescimento & desenvolvimento , Óxido de Zinco/uso terapêutico , Animais , Antibacterianos/efeitos adversos , Antibacterianos/análise , Antibacterianos/química , Antibacterianos/uso terapêutico , Antidiarreicos/efeitos adversos , Antidiarreicos/análise , Antidiarreicos/química , Antidiarreicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Diarreia/etiologia , Diarreia/microbiologia , Diarreia/prevenção & controle , Diarreia/veterinária , Digestão , Ingestão de Energia , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fezes/microbiologia , Feminino , Trato Gastrointestinal/crescimento & desenvolvimento , Trato Gastrointestinal/microbiologia , Glucanos , Masculino , Polissacarídeos/efeitos adversos , Polissacarídeos/análise , Polissacarídeos/metabolismo , Polissacarídeos/uso terapêutico , Sus scrofa/metabolismo , Sus scrofa/microbiologia , Desmame , Aumento de Peso , Óxido de Zinco/efeitos adversos
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