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BACKGROUND: We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification. PATIENTS AND METHODS: A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR). For exploratory analyses, we analyzed the gene profiles using plasma NGS test. RESULTS: Thirty-five patients were enrolled. The ORR was 57.6% for all patients, 52.2% for those with METex14, and 70% for those with MET amplification. Median progression-free survival (PFS) was 8 months [95% confidence interval (CI) 4.5-11.5 months] and median overall survival (OS) was 14 months (95% CI 7.8-20.2 months) in all patients. For patients with non-small-cell lung cancer with METex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months [95% CI not applicable (NA)-NA]. For patients with MET amplification, the median PFS was 7 months (95% CI 1.5-12.5 months) and the median OS was 10 months (95% CI 5.8-14.2 months). The ORR of patients with MET dysregulation detected by plasma NGS was 72.2%, whereas the ORR was 30% in those without detection. The most common adverse events were peripheral edema, asthenia, transaminase elevation, and anorexia, mostly grade 1 or 2. CONCLUSIONS: Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.
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AIM: To evaluate the change in diagnosis rates, disease severity at presentation, and treatment of acute appendicitis and diverticulitis during the COVID-19 shutdown. MATERIALS AND METHODS: Following institutional review board approval, 6,002 CT examinations performed at five hospitals for suspected acute appendicitis and/or diverticulitis over the 12 weeks preceding and following the shutdown were reviewed retrospectively. Semi-automated language analysis (SALA) of the report classified 3,676 CT examinations as negative. Images of the remaining 2,326 CT examinations were reviewed manually and classified as positive or negative. Positive cases were graded as non-perforated; perforated, contained; and perforated, free. RESULTS: CT examinations performed for suspected appendicitis and/or diverticulitis decreased from 3,558 to 2,200 following the shutdown. The rates of positive diagnoses before and after shutdown were 4% (144) and 4% (100) for appendicitis and 8% (284) and 7% (159) for diverticulitis (p>0.2 for both). For positive CT examinations, the rates of perforation, hospitalisation, surgery, and catheter drainage changed by -2%, -3%, -2%, and -3% for appendicitis (n=244, p>0.3 for all) and +6% (p=0.2) +9% (p=0.06), +4% (p=0.01) and +1% (p=0.6) for diverticulitis (n=443). CONCLUSION: CT examinations performed for suspected appendicitis or diverticulitis declined after the shutdown, likely reflecting patients leaving urban centres and altered triage of non-COVID-19 patients. The diagnosis rates, disease severity at presentation, and treatment approach otherwise remained mostly unchanged.
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Apendicite , COVID-19 , Diverticulite , Doença Aguda , Apendicite/diagnóstico por imagem , Apendicite/cirurgia , COVID-19/diagnóstico por imagem , Diverticulite/diagnóstico por imagem , Diverticulite/cirurgia , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
Oncology has progressed into an era of personalised medicine, whereby the therapeutic regimen is tailored to the molecular profile of the patient's cancer. Determining personalised therapeutic options is achieved by using tumour genomics and proteomics to identify the specific molecular targets against which candidate drugs can interact. Several dozen targeted drugs, many for multiple cancer types are already widely in clinical use. Molecular profiling of tumours is contingent on high-quality biopsy specimens and the most common method of tissue sampling is image-guided biopsy. Thus, for radiologists performing these biopsies, the paradigm has now shifted away from obtaining specimens simply for histopathological diagnosis to acquiring larger amounts of viable tumour cells for DNA, RNA, or protein analysis. These developments have highlighted the central role now played by radiologists in the delivery of personalised cancer care. This review describes the principles of molecular profiling assays and biopsy techniques for optimising yield, and describes a scoring system to assist in patient selection for percutaneous biopsy.
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Diagnóstico por Imagem/métodos , Genômica/métodos , Neoplasias/genética , Neoplasias/patologia , Medicina de Precisão/métodos , Biomarcadores Tumorais , Humanos , Biópsia Guiada por Imagem , Neoplasias/diagnóstico por imagemRESUMO
AIM: Intussusception in adults is rare and requires surgery in most cases. While abdominal laparoscopic surgery (LS) is becoming more popular, there are few reports on the outcomes of adult intussusception treated with LS. This study compared the feasibility of LS vs open surgery (OS) for adult intussusception. METHOD: We reviewed retrospectively the medical records of adult patients with intussusception from three tertiary hospitals between 2000 and 2016. The patients were divided into LS and OS groups, and their surgical outcomes were compared. RESULTS: Surgery was indicated in 71 patients with intussusception (41 LS and 30 OS). The median age of the patients was 49.0 and 51.5 years in the LS and OS groups, respectively (P = 0.930). Overall, nine (12.7%) patients had a negative laparotomy or laparoscopy with spontaneous reduction of the intussusception. Conversion to OS from LS was necessary in one patient (2.4%). The operative time and intra-operative and postoperative complication rates were not significantly different. However, there were more serious complications such as bowel perforation and major vessel injury in the LS group. The patients in the LS group had a shorter time to first food intake and hospital stay vs patients in the OS group (4.0 vs 6.0 days, P < 0.001, and 7.0 vs 10.5 days, P < 0.001, respectively). CONCLUSION: LS may be feasible for adult intussusception; there may be more severe intra-operative complications than in OS.
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Intussuscepção , Laparoscopia , Adulto , Humanos , Recém-Nascido , Intussuscepção/cirurgia , Tempo de Internação , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Esplenectomia , Resultado do TratamentoRESUMO
BACKGROUND: Cellulitis can be a difficult diagnosis to make. Furthermore, 31% of patients admitted from the emergency department with suspected lower-limb cellulitis have been misdiagnosed, with incorrect treatment potentially resulting in avoidable hospital admission and the prescription of unnecessary antibiotics. OBJECTIVES: We sought to identify diagnostic criteria or tools that have been developed for lower-limb cellulitis. METHODS: We conducted a systematic review using Ovid MEDLINE and Embase databases in May 2018, with the aim of describing diagnostic criteria and tools developed for lower-limb cellulitis, and we assessed the quality of the studies identified using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We included all types of study that described diagnostic criteria or tools. RESULTS: Eight observational studies were included. Five studies examined biochemical markers, two studies assessed imaging and one study developed a diagnostic decision model. All eight studies were considered to have a high risk for bias in at least one domain. The quantity and quality of available data was low and results could not be pooled owing to the heterogeneity of the findings. CONCLUSIONS: There is a lack of high-quality publications describing criteria or tools for diagnosing lower-limb cellulitis. Future studies using prospective designs, validated in both primary and secondary care settings, are needed. What's already known about this topic? Diagnosing lower-limb cellulitis on first presentation is challenging. Approximately one in three patients admitted from the emergency department with suspected lower-limb cellulitis do not have cellulitis and are given another diagnosis on discharge. Consequently, this results in potentially avoidable hospital admissions and the prescription of unnecessary antibiotics. There are no diagnostic criteria available for lower-limb cellulitis in the U.K. What does this study add? This systematic review has identified a key research gap in the diagnosis of lower-limb cellulitis. There is a current lack of robustly developed and validated diagnostic criteria or tools for use in clinical practice.
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Celulite (Flegmão)/diagnóstico , Antibacterianos/uso terapêutico , Biomarcadores/análise , Celulite (Flegmão)/tratamento farmacológico , Técnicas de Apoio para a Decisão , Erros de Diagnóstico/prevenção & controle , Humanos , Extremidade Inferior , Estudos Observacionais como Assunto , Admissão do Paciente , Tempo para o TratamentoRESUMO
BACKGROUND: Presentations of suspected lower-limb cellulitis are commonly misdiagnoses, resulting in avoidable antibiotic prescribing or hospital admissions. Understanding the challenges posed in diagnosing cellulitis may help enhance future care. OBJECTIVES: To examine and map out the challenges and facilitators identified by patients and health professionals in diagnosing lower-limb cellulitis. METHODS: A scoping systematic review was performed in MEDLINE and Embase in October 2017. Thematic analysis was used to identify key themes. Quantitative data were summarized by narrative synthesis. RESULTS: Three themes were explored: (i) clinical case reports of misdiagnosis, (ii) service development and (iii) diagnostic aids. Forty-seven different pathologies were misdiagnosed, including seven malignancies. Two different services have been piloted to reduce the misdiagnosis rates of lower-limb cellulitis and save costs. Four studies have looked at biochemical markers, imaging and a scoring tool to aid diagnosis. CONCLUSIONS: This review highlights the range of alternative pathologies that can be misdiagnosed as cellulitis, and emerging services and diagnostic aids developed to minimize misdiagnosis. Future work should focus on gaining a greater qualitative understanding of the diagnostic challenges from the perspective of patients and clinicians.
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Celulite (Flegmão)/diagnóstico , Erros de Diagnóstico/prevenção & controle , Adipose Dolorosa/diagnóstico , Celulite (Flegmão)/sangue , Celulite (Flegmão)/patologia , Pé Diabético/diagnóstico , Diagnóstico Diferencial , Gota/diagnóstico , Humanos , Perna (Membro) , Pele/patologiaRESUMO
This study examined the effects of dietary Spirulina (Arthrospira) platensis supplementation on growth performance, antioxidant enzyme activity, nutrient digestibility, cecal microflora, excreta noxious gas emission, organ weight and breast meat quality in broiler chickens. In total, 800 Ross 308 male broiler chickens (1-d-old) were randomly divided into 5 dietary treatments with 10 replicate cages (16 birds/replicate) per treatment for 5 wk. The dietary treatments were a control basal diet without Spirulina or with 0.25, 0.5, 0.75, or 1.0% Spirulina. Body weight gain, feed conversion, and/or European production efficiency index improved linearly with supplementation of Spirulina during d 8 to 21, 22 to 35, and overall d 1 to 35 (P < 0.05). Dietary Spirulina supplementation caused a significant increase in the serum enzyme activity of superoxide dismutase and glutathione peroxidase (linear, P < 0.05). Apparent total tract digestibility of dry matter and nitrogen showed a linear increase in Spirulina supplementation (P < 0.05). Cecal Lactobacillus count linearly increased and excreta ammonia gas emission linearly decreased, as dietary Spirulina supplementation increased (P < 0.05). There were no significant effects on relative organ weight and breast meat quality of broilers fed with Spirulina diets; however, 7 d drip loss linearly decreased in treatment groups fed with Spirulina (P < 0.05). These results indicate that adding Spirulina to the diet of broilers can improve antioxidant enzyme activity, dry matter and nitrogen digestibility, cecal Lactobacillus population, excreta ammonia gas emission, and 7 d drip loss of breast meat. In addition, dietary inclusion of 1.0% Spirulina powder might provide a good alternative to improve broiler chicken production.
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Antioxidantes/metabolismo , Ceco/microbiologia , Galinhas/microbiologia , Galinhas/fisiologia , Digestão/efeitos dos fármacos , Carne/análise , Spirulina/química , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Fezes/química , Gases/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Músculos Peitorais/fisiologia , Distribuição AleatóriaRESUMO
Our objective of this study was to explore the bacterial microbiome in fresh or fresh-frozen adult Amblyomma maculatum (Gulf Coast ticks) using extracts enriched for microbial DNA. We collected 100 questing adult A. maculatum, surface disinfected them, and extracted DNA from individual ticks collected the same day or after storage at -80⯰C. Because only extracts with microbial DNA concentrations above 2â¯ng/µL were considered suitable for individual analysis, we expected fewer samples to meet these requirements. Of individual ticks extracted, 48 extracts met this minimum concentration. We pooled 20 additional extracts that had lower concentrations to obtain seven additional pools that met the minimum DNA concentration. Libraries created from these 55 samples were sequenced using an Illumina MiSeq platform, and data sets were analyzed using QIIME to identify relative abundance of microorganisms by phylum down to genus levels. Proteobacteria were in greatest abundance, followed by Actinobacteria, Firmicutes, and Bacteroidetes, at levels between 1.9% and 6.4% average relative abundance. Consistent with the Francisella-like endosymbiont known to be present in A. maculatum, the genus Francisella was detected at highest relative abundance (72.9%; SE 0.02%) for all samples. Among the top ten genera identified (relative abundanceâ¯≥â¯0.5%) were potential extraction kit contaminants, Sphingomonas and Methylobacterium, the soil bacterium Actinomycetospora, and the known A. maculatum-associated genus, Rickettsia. Four samples had Rickettsia at greater than 1% relative abundance, while nine additional samples had Rickettsia at low (0.01-0.04%) relative abundance. In this study, we used the entire microbe-enriched DNA extract for whole ticks for microbiome analysis. A direct comparison of the microbiome in microbe-enriched DNA and total genomic DNA extracts from halves of the same tick would be useful to determine the utility of this extraction method in this system. We anticipate that future tick microbiome studies will be valuable to explore the influence of microbial diversity on pathogen maintenance and transmission, and to evaluate niche-specific microbiomes within individual tick tissues.
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Ixodidae/microbiologia , Microbiota/genética , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Animais , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Francisella/genética , Francisella/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Mississippi/epidemiologia , Filogenia , Proteobactérias/genética , Proteobactérias/isolamento & purificação , Rickettsia/genética , Infestações por Carrapato/epidemiologia , Extratos de TecidosRESUMO
AIM: Residual ß-cell function is present at the time of diagnosis with Type 1 diabetes. Preserving this ß-cell function reduces complications. We hypothesized that exercise preserves ß-cell function in Type 1 diabetes and undertook a pilot trial to address the key uncertainties in designing a definitive trial to test this hypothesis. METHODS: A randomized controlled pilot trial in adults aged 16-60 years diagnosed with Type 1 diabetes within the previous 3 months was undertaken. Participants were assigned to control (usual care) or intervention (exercise consultation every month), in a 1 : 1 ratio for 12 months. The primary outcomes were recruitment rate, drop out, exercise adherence [weeks with ≥ 150 min of self-reported moderate to vigorous physical activity (MVPA)], and exercise uptake in the control group. The secondary outcomes were differences in insulin sensitivity and rate of loss of ß-cell function between intervention and control at 6 and 12 months. RESULTS: Of 507 individuals who were approached, 58 (28 control, 30 intervention) entered the study and 41 completed it. Participants were largely white European males, BMI 24.8 ± 3.8 kg/m2 , HbA1c 75 ± 25 mmol/mol (9 ± 2%). Mean level of objectively measured MVPA increased in the intervention group (mean 243 to 273 min/week) and 61% of intervention participants reached the target of ≥ 150 min/week of self-reported MVPA on at least 42 weeks of the year. Physical activity levels fell slightly in the control group (mean 277 to 235 min of MVPA/week). There was exploratory evidence that intervention group became more insulin sensitive and required less insulin. However, the rate of loss of ß-cell function appeared similar between the groups, although the change in insulin sensitivity may have affected this. CONCLUSION: We show that it is possible to recruit and randomize people with newly diagnosed Type 1 diabetes to a trial of an exercise intervention, and increase and maintain their exercise levels for 12 months. Future trials need to incorporate measures of greater adherence to exercise training targets, and include more appropriate measures of ß-cell function. (Clinical Trials Registry No; ISRCTN91388505).
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Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/terapia , Exercício Físico/fisiologia , Células Secretoras de Insulina/fisiologia , Adolescente , Adulto , Idade de Início , Diabetes Mellitus Tipo 1/metabolismo , Terapia por Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto JovemRESUMO
The aim of this research was to optimize two multiplex polymerase chain reaction (PCR) assays that could simultaneously detect six non-O157 Shiga toxin-producing Escherichia coli (STEC) as well as the three virulence genes. We also investigated the potential of combining the FTA™ card-based DNA extraction with the multiplex PCR assays. Two multiplex PCR assays were optimized using six primer pairs for each non-O157 STEC serogroup and three primer pairs for virulence genes respectively. Each STEC strain specific primer pair only amplified 155, 238, 321, 438, 587 and 750 bp product for O26, O45, O103, O111, O121 and O145 respectively. Three virulence genes were successfully multiplexed: 375 bp for eae, 655 bp for stx1 and 477 bp for stx2. When two multiplex PCR assays were validated with ground beef samples, distinctive bands were also successfully produced. Since the two multiplex PCR examined here can be conducted under the same PCR conditions, the six non-O157 STEC and their virulence genes could be concurrently detected with one run on the thermocycler. In addition, all bands clearly appeared to be amplified by FTA card DNA extraction in the multiplex PCR assay from the ground beef sample, suggesting that an FTA card could be a viable sampling approach for rapid and simple DNA extraction to reduce time and labour and therefore may have practical use for the food industry. SIGNIFICANCE AND IMPACT OF THE STUDY: Two multiplex polymerase chain reaction (PCR) assays were optimized for discrimination of six non-O157 Shiga toxin-producing Escherichia coli (STEC) and identification of their major virulence genes within a single reaction, simultaneously. This study also determined the successful ability of the FTA™ card as an alternative to commercial DNA extraction method for conducting multiplex STEC PCR assays. The FTA™ card combined with multiplex PCR holds promise for the food industry by offering a simple and rapid DNA sample method for reducing time, cost and labour for detection of STEC in food and environmental samples.
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Adesinas Bacterianas/genética , Proteínas de Escherichia coli/genética , Análise de Perigos e Pontos Críticos de Controle/métodos , Toxina Shiga I/genética , Toxina Shiga II/genética , Escherichia coli Shiga Toxigênica/genética , Escherichia coli Shiga Toxigênica/patogenicidade , Animais , Bovinos , Primers do DNA , Microbiologia de Alimentos/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Carne Vermelha/microbiologia , Virulência/genéticaRESUMO
This 5-week study was conducted to determine the effects of Enterococcus faecium (SLB 120) on growth performance, blood parameters, relative organ weight, breast muscle meat quality, excreta microbiota shedding, and noxious gas emission in broilers. A total of 816 one-day-old male broilers were allocated to 4 groups with 12 replications (17 broilers/pen) according to body weight (43.2 ± 0.32 g). Dietary treatment groups were: (1) CON, basal diet, (2) T1, CON + 0.05% E. faecium, (3) T2, CON + 0.10% E. faecium, (4) T3, CON + 0.20% E. faecium. From day 1 to 21, dietary E. faecium supplementation showed linear increase (P < 0.05) in gain:feed ratio. From day 21 to 35 and the overall period, dietary E. faecium supplementation showed a linear increase (P < 0.05) in body weight gain and gain:feed ratio. On day 35, dietary E. faecium supplementation showed a linear increase (P < 0.05) in the apparent total tract digestibility of dry matter and nitrogen, and the relative weight of bursa of Fabricius; no differences were observed in white blood cells, red blood cells or lymphocyte counts. Dietary E. faecium supplementation showed a linear decrease (P < 0.05) in excreta E.coli counts on day 7 and 35, while excreta Lactobacillus counts were linearly increased (P < 0.05) on day 35. On day 35, dietary E. faecium supplementation linearly decreased (P < 0.05) excreta NH3, H2S, and total mercaptans emission, but only H2S emission was linearly decreased (P < 0.05) on day 7. In conclusion, the supplementation of E. faecium improved growth performance, the digestibility of dry matter and nitrogen, the relative weight of bursa of Fabricius, and shifted excreta microbiota by increasing Lactobacillus and decreasing E.coli counts, as well as decreased excreta NH3, H2S, and total mercaptans gas emission.
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Poluentes Atmosféricos/metabolismo , Galinhas/fisiologia , Enterococcus faecium/classificação , Fezes/microbiologia , Carne/análise , Probióticos/farmacologia , Amônia/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Galinhas/sangue , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Sulfeto de Hidrogênio/metabolismo , Masculino , Tamanho do Órgão , Músculos Peitorais/fisiologia , Probióticos/administração & dosagem , Distribuição Aleatória , Compostos de Sulfidrila/metabolismoRESUMO
Supplementation of poultry diets with Diamond V Original XPC™ (XPC) has been proposed as a means to ameliorate the commonly observed loss of appetite and depression of growth in birds given a live coccidiosis vaccine. A study was conducted to compare the effects on bird performance of a live coccidiosis vaccine in broilers, with and without the dietary inclusion of XPC (1.25 g/kg). Ross 708 male broilers (n = 1,280) were allocated to one of 4 feed treatments: cocci-vaccine (T1), cocci-vaccine + XPC (T2), cocci-vaccine + salinomycin in the grower diet only, (T3), and cocci-vaccine + salinomycin in the grower diet + XPC (T4). Birds consuming diets containing XPC (T2 and T4) and salinomycin (T3) exhibited increased (P < 0.05) feed intake and significantly heavier body weights at 28 d (1.70, 1.74, and 1.67 kg, respectively) and 42 d (3.29, 3.31, and 3.26 kg, respectively). Feed conversion ratio at 28 d was improved (P < 0.05) by adding XPC to diets (T2: 1.47 and T4: 1.44) compared to control diets (T1: 1.50 and T3: 1.47). Salmonella prevalence determined via selective media indicated the inclusion of XPC in the diet resulted in a significant reduction of Salmonella when compared to treatments lacking XPC. Molecular confirmation of Salmonella species indicated S. Kentucky to be present in 38 of the 39 positive samples. Results revealed the ability of XPC in reducing the prevalence of Salmonella. Results from this study also suggest that XPC could be used in conjunction with a live coccidiosis-vaccine to increase growth rate and improve feed conversion of broilers. However, further work is needed to delineate more specific effects directly attributable to XPC.
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Galinhas/imunologia , Suplementos Nutricionais , Salmonelose Animal/tratamento farmacológico , Salmonella/efeitos dos fármacos , Vacinas Atenuadas/administração & dosagem , Ração Animal/análise , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/microbiologia , Coccidiose/prevenção & controle , Coccidiose/veterinária , Dieta/veterinária , Masculino , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/prevenção & controle , Piranos/administração & dosagem , Piranos/farmacologia , Salmonelose Animal/prevenção & controleRESUMO
PURPOSE: This multi-center, randomized, phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia (DSN). METHODS: Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) were enrolled. All participants were randomized to receive either daily subcutaneous injections of filgrastim 100 µg/m2/day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle. RESULTS: The mean duration of grade 4 (G4) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group. The difference between groups was 0.2 ± 1.10 days (95 % confidence interval (CI) = -0.26, 0.66), which supported non-inferiority. No statistically significant differences were observed in nadir absolute neutrophil count (ANC) (154.34/mm3 and 161.75/mm3 for the filgrastim and DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups, respectively; P = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was determined to be related to the study drug. CONCLUSIONS: DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy.
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Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Filgrastim/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/etiologia , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Ciclofosfamida/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Filgrastim/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Taxoides/administração & dosagemRESUMO
This study was designed to evaluate the effects of two different complex probiotic supplementations on the growth performance, meat quality, excreta microflora, nutrient retention, blood metabolic profile and noxious gas emissions in broilers. A total of 612 conventional healthy 1-d-old Ross 308 broilers with body weight of 41 ± 0.3 g were randomly divided into 3 treatments with 12 replicate cages, with 17 broilers in each cage and fed with the following diets: CON-Basal diet, T1-CON + Probiotic A, T2-CON + Probiotic B. Significant results were observed on body weight gain, but not on feed conversation ratio and feed intake, in the whole experimental period. Increased faecal lactobacillus counts were found with probiotics supplementation. However, no significant effects were found for meat quality, nutrient retention, blood metabolic profile or noxious gas emissions. In conclusion, both multi-strain probiotics had beneficial effects on growth performance, drip loss percentage and faecal Lactobacillus counts in broilers.
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Galinhas/microbiologia , Galinhas/fisiologia , Dieta/veterinária , Probióticos/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Carga Bacteriana , Ingestão de Alimentos/fisiologia , Fezes/microbiologia , Feminino , Lactobacillus , Masculino , Carne/análise , Aumento de PesoRESUMO
This experiment was conducted to investigate the efficacy of multistrain probiotics in weaning pigs. A total of 125 28-day-old weaning pigs [(Landrace × Yorkshire) × Duroc] with an initial average body weight (BW) of 7.26 ± 0.76 kg were randomly allotted into 5 treatments, 5 replicate pens/treatment with 5 pigs/pen for 42-day experiment. Dietary treatments were as follows: CON, basal diet; PC1, CON + 0.01% multistrain probiotics; PC2, CON + 0.03% multistrain probiotics; PC3, CON + 0.06% multistrain probiotics; PC4, CON + 0.1% multistrain probiotics. On day 14, pigs fed the PC4 diet had higher BW gain than pigs fed the CON diet. On day 42, pigs fed multistrain probiotics supplementation diets had higher BW gain than pigs fed the CON diet. From days 1 to 14, pigs fed the PC2, PC3 and PC4 diets had higher (p < 0.05) ADG than pigs fed the CON diet. From day 15 to 42, pigs fed the multistrain probiotics supplementation diets had higher (p < 0.05) average daily gain (ADG) and gain: feed ratio (G:F) than pigs fed the CON diet. In the overall period, pigs fed the multistrain probiotics supplementation diets had higher (p < 0.05) ADG and pigs fed the PC2 and PC4 diets had higher (p < 0.05) G:F than pigs fed the CON diet. On day 42, pigs fed the PC4 diet had higher (p < 0.05) apparent total tract digestibility (ATTD) of dry matter (DM), nitrogen (N) and gross energy (GE), faecal Lactobacillus counts and lower (p < 0.05) E. coli counts and NH3 emission than pigs fed the CON diet. Pigs fed the multistrain probiotics supplementation diets had lower (p < 0.05) H2 S and total mercaptans emissions than pigs fed the CON diet. Conclusions, dietary supplementation with 0.1% probiotics improved growth performance, nutrition digestibility and intestinal microflora balance and decreased faecal noxious gas emissions in weaning pigs.
Assuntos
Digestão/fisiologia , Fezes/microbiologia , Probióticos/farmacologia , Suínos/fisiologia , Animais , Fezes/química , Gases , Probióticos/classificação , Suínos/sangue , DesmameRESUMO
BACKGROUND: It remains to be elucidated whether exposure to air pollutants aggravates atopic dermatitis (AD). OBJECTIVES: This study aimed to evaluate the effects of exposure to formaldehyde for 1 h and 2 h on skin barrier function in both the control and the AD groups. METHODS: In 41 patients with AD and 34 healthy children, a provocation test was performed in which two different areas of normal-appearing skin on the forearm were stimulated with airborne formaldehyde at 500 µg m(-3) or placebo for 2 h. We measured transepidermal water loss (TEWL) and skin pH, and calculated the percentage change from baseline. RESULTS: Exposure to formaldehyde increased TEWL in the control group [P < 0·001; median of difference 1·4; interquartile range (IQR) 0·9-1·6] and in the AD group (P < 0·001; median of difference 2·5; IQR 2·0-3·6). The percentage change of TEWL after formaldehyde exposure in the AD group was higher than in the control group (P < 0·001), whereas exposure to placebo showed no differences between both groups. The AD group also demonstrated a higher percentage increase in skin pH after exposure to formaldehyde than the control group (P < 0·001). CONCLUSIONS: Short-term exposure to formaldehyde causes skin barrier dysfunction in both healthy children and children with AD, and this effect is more prominent in children with AD.
Assuntos
Poluentes Atmosféricos/toxicidade , Dermatite Atópica/fisiopatologia , Formaldeído/toxicidade , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Desenho de Equipamento , Feminino , Antebraço , Humanos , Concentração de Íons de Hidrogênio , Masculino , Testes Cutâneos/instrumentação , Testes Cutâneos/métodos , Perda Insensível de Água/efeitos dos fármacosRESUMO
The ban on the use of antibiotics as growth promoters due to resistance issues has urged scientists to find alternatives to antibiotics. Entercoccus faecium is one of the probiotics which have been used as an alternative to antibiotics in the livestock industry. This study was conducted to evaluate the effect of probiotic (Enterococcus faecium DSM 7134) supplementation on production performance, feed intake, egg quality, excreta microflora, ammonia emission, and nutrient utilization in laying hens. A total of 288 ISA brown laying hens were used in a 27 wk feeding experiment and randomly assigned to 3 dietary treatments with 8 replicates of 12 birds each. The treatments were CON (basal diet), PB1 (basal diet + 0.005% E. faecium), and PB2 (basal diet + 0.01% E. faecium). Overall, our results demonstrated that E. faecium supplementation resulted in a significant increase in egg production, egg shell thickness, and nutrient digestibility (dry matter, nitrogen, and energy) in laying hens, and a significant reduction in fecal coliform counts as compared with CON. The shift of excreta fecal microbial composition by E. faecium supplementation was accompanied by increased nutrient retention and reduction in nutrient excretion, leading to improved nutrient digestibility and reduced excreta ammonia emission. Overall, E. faecium supplementation appears to have a beneficial effect in ISA brown laying hens and should be considered as a positive diet supplement to use in the industry.
Assuntos
Amônia/metabolismo , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Galinhas/fisiologia , Suplementos Nutricionais , Enterococcus faecium/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Oviposição/efeitos dos fármacos , Probióticos/farmacologia , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Animais , Dieta/veterinária , Ovos/normas , Feminino , Oviposição/fisiologiaRESUMO
Chicken serum has been suggested as a supplement to promote chicken cell proliferation and development. However, the molecular mechanisms by which chicken serum stimulates chicken cell proliferation remain unknown. Here, we evaluated the effects of chicken serum supplementation on chicken embryo fibroblast (CEF) and DF-1 cell proliferation. We also sought to elucidate the molecular pathways involved in mediating the effects of chicken serum on fibroblasts and DF-1 cells by overexpression of chicken 78 kDa glucose-regulated protein (chGRP78), which is important for cell growth and the prevention of apoptosis. Our data demonstrated that the addition of 5% chicken serum significantly enhanced fibroblast proliferation. Moreover, knockdown of chGRP78 using siRNA decreased fibroblast proliferation and increased apoptosis. Based on these results, we suggest that the chGRP78-mediated signaling pathway plays a critical role in chicken serum-stimulated fibroblast survival and anti-apoptosis. Therefore, our findings have important implications for the maintenance of chicken fibroblast cells through the inhibition of apoptosis and may lead to the development of new treatments for avian disease.
Assuntos
Apoptose/fisiologia , Proliferação de Células , Fibroblastos/fisiologia , Regulação da Expressão Gênica/fisiologia , Proteínas de Choque Térmico/metabolismo , Animais , Células Cultivadas , Embrião de Galinha , Chaperona BiP do Retículo Endoplasmático , Fibroblastos/metabolismo , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico/genética , Interferência de RNA , RNA Interferente PequenoRESUMO
BACKGROUND: Autophagy and genetic predisposition have been suggested to potentially play roles in the development of asthma. However, little is known about the role of autophagy in the pathogenesis of severe asthma. OBJECTIVE: We compared autophagy in the sputum granulocytes, peripheral blood cells (PBCs) and peripheral blood eosinophils (PBEs) between patients with severe asthma and those with non-severe asthma and investigated the functional effects of autophagy. METHODS: We enrolled 36 patients with severe asthma, 14 with non-severe asthma and 23 normal healthy controls in this study. Sputum granulocytes, PBCs and PBEs were isolated from each subject. Autophagy was evaluated based on the expression of microtubule-associated protein light chain 3 (LC3) by Western blot, confocal microscopy, transmission electron microscopy and flow cytometry. IL-8 levels were measured by ELISA. To induce autophagy, HL-60 cells, human primary small airway epithelial cells (SAECs) and A549 cells were treated with IL-5, IL-1ß and TNF-α. To inhibit autophagy, PI3K inhibitors (LY29400 and 3-methyladenine [3-MA]) and hydroxychloroquine (HCQ) were used. Knockdown of ATG5 and Beclin-1 was performed in A549 cells, and the therapeutic effects of dexamethasone were evaluated. RESULTS: Higher autophagy levels were noted in sputum granulocytes, PBCs and PBEs from patients with severe asthma than from patients with non-severe asthma and healthy controls (P < 0.05 for all). IL-5 increased autophagy levels in both PBCs and PBEs (P < 0.05). 3-MA attenuated the increased expression of LC3-II and eosinophil cationic protein in HL-60 cells induced by IL-5 (P = 0.034 for both). Dexamethasone did not affect autophagy levels in PBEs. IL-1ß increased LC3-II expression and IL-8 production (P < 0.01) in SAECs, and this was attenuated by LY294002, 3-MA, HCQ and knockdown of ATG5 and Beclin-1 (in A549 cells) (P < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Autophagy could play a role in the pathogenesis of severe asthma. Autophagy modulation may be a novel therapeutic target for conventional therapy-resistant severe asthma.
Assuntos
Asma/etiologia , Asma/metabolismo , Autofagia , Leucócitos/imunologia , Leucócitos/metabolismo , Escarro/citologia , Escarro/imunologia , Adulto , Proteínas Reguladoras de Apoptose/genética , Asma/diagnóstico , Asma/terapia , Proteína 5 Relacionada à Autofagia , Proteína Beclina-1 , Estudos de Casos e Controles , Linhagem Celular , Citocinas , Feminino , Volume Expiratório Forçado , Técnicas de Silenciamento de Genes , Granulócitos/imunologia , Granulócitos/metabolismo , Humanos , Imunoglobulina E/imunologia , Contagem de Leucócitos , Masculino , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Fagossomos/metabolismo , Índice de Gravidade de Doença , Adulto JovemRESUMO
Phytogenic feed additives have become attractive alternatives for use in animal diets. The objective of the present study was to evaluate the effect of a phytogenic-based feed additive on growth performance, nutrient digestibility, blood profiles, fecal noxious gas emission, and intestinal morphology of weaning pigs after dietary challenge with E. coli K88. A total of 120 crossbred pigs [(Yorkshire×Landrace)×Duroc)] with an initial body weight (BW) of 6.09±0.96 kg (21 d of age) were assigned randomly to 1 of the 4 dietary treatments. Each pen housed 5 pigs, and there were 6 pens/treatment. Treatments included: T1, negative control (without antibiotics); T2, T1+antibiotic; T3, T1+0.05% phytogenics; and T4, T1+0.2% commercial mix of organic acids. Overall, the average daily gain (ADG) with the T3 treatment was higher (P<0.05). At wk 1, the apparent total tract digestibility (ATTD) of dry matter (DM) was increased (P<0.05) with T4 treatment. The ATTD of ash with T3 and T4 treatments was greater (P<0.05). At wk 3, pigs fed with the T4 diet had a significantly higher (P<0.05) ATTD of DM. The ATTD of ash and calcium (Ca) was significantly increased (P<0.05) with the T4 treatment. Pigs fed with the T3 diet had a higher (P<0.05) ATTD of phosphorus (P). At wk 6, the ATTD of ash was significantly increased (P<0.05) with the T1 and T3 treatments. The data indicate that phytogenics positively affect growth performance of weaning pigs, indicating that their use as an alternative in the diets of weaning pigs can significantly improve ADG, under challenge with E.coli K88.