Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 235
Filtrar
1.
Animal ; 18(6): 101174, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38761441

RESUMO

The dynamics of cattle body chemical composition during growth and fattening periods determine animal performance and beef carcass quality. The aim of this study was to estimate the empty body (EB) and carcass chemical composition of growing beef-on-dairy crossbred bulls (Brown Swiss breed as dam with Angus, Limousin or Simmental as sire) using three-dimensional (3D) imaging. The 3D images of the cattle's external body shape were recorded in vivo on 48 bulls along growth trajectory (75-520 kg BW and 34-306 kg hot carcass weight [HCW]; set 1) and on 70 bulls at target market slaughter weight, including 18 animals from set 1 (average 517 ± 10 kg BW and 289 ± 10 kg HCW; set 2). The linear, circumference, curve, surface and volume measurements on the 3D body shape were determined. Those predictive variables were used in partial least square regressions, together with the effect of the sire breed whenever significant (P < 0.05), with leave-one-out cross-validation to estimate water, lipid, protein, mineral and energy mass or proportions in the EB and carcass. Mass and proportions were determined directly from postmortem grinding and chemical analyses (set 1) or indirectly using the 11th rib dissection method (set 2). In set 1, bulls' BW and HCW were estimated via 3D imaging, with root mean square error of prediction (RMSEP) of 12 kg and 6 kg, respectively. The EB and carcass chemical component proportions were estimated with RMSEP from 0.2% for EB minerals (observed mean 3.7 ± 0.2%) to 1.8% for EB lipid (11.6 ± 4.2%), close to the RMSEP found for the carcass. In set 2, the RMSEP for estimation via 3D imaging was 9 kg for BW and 6 kg for HCW. The EB energy and protein proportions were estimated, with RMSEP of 0.5 MJ/kg fresh matter (10.1 ± 0.8 MJ/DM) and 0.2% (18.7 ± 0.7%), respectively. Overall, the estimations of chemical component proportions from 3D imaging were slightly less precise for both sets than the mass estimations. The morphological traits from the 3D images appeared to be precise estimators of BW, HCW as well as EB and carcass chemical component masses and proportions.

2.
J Dairy Sci ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38490553

RESUMO

The effect of the horn status of cows on their milk composition and quality is a controversial research topic. In this study, 128 milk samples from 64 horned and 64 disbudded Brown Swiss and Original Braunvieh cows were collected from alpine farms where both horned and disbudded cows were grazing on mountain pastures. The samples were analyzed for their detailed composition and protein digestion in a simulated in vitro digestion (INFOGEST). To exclude probable influences on digestion, the ß-casein genotype with its variants A1 and A2 was also included in the study. The effects of horn status and ß-casein genotype were investigated in linear mixed models, which included additional influencing random factors such as Original Braunvieh blood proportion, stage of lactation, and farm. Horn status did not have any effect on milk composition or digestion. In contrast, milk from A1A1 cows showed a different protein digestion than milk of A1A2 and A2A2 cows in the gastric phase, including smaller amounts of ß-casomorphin(BCM)21-associated peptides and larger amounts of BCM11-associated peptides. Abundances of BCM7 did not differ between ß-casein genotypes. At the end of the intestinal phase, the digested milk of A1A1 and A2A2 b-casein genotypes did not differ.

3.
Animal ; 18(3): 101097, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38401327

RESUMO

Exposure to direct solar radiation, high ambient temperature, lack of wind movement, coupled with own metabolic heat production, makes grazing dairy cows vulnerable to heat stress. In pastures, it would be beneficial to monitor heat stress by observable changes in behaviour. We hypothesised that grazing dairy cows exhibit behavioural changes due to increasing heat load in temperate climate. Over two consecutive summers, 38 full-time grazing Holstein dairy cows were investigated in 12 experimental periods of up to 3 consecutive days where the cows were repeatedly exposed to various levels of moderate heat load determined by the comprehensive climate index (CCI). The CCI defines the ambient climate conditions, combining air temperature, relative humidity, solar radiation and wind speed. Vaginal temperature (VT) was automatically measured as an indicator of heat stress. In addition, as a less invasive method, we investigated if reticular temperature (RET) can be indicative of heat stress on pastures. Walking activity, lying-, feeding, and ruminating durations were recorded continuously with sensors. Respiration rate (RR), proximity to and competition at the water trough, social licking, self-licking, inter-individual distance, and fly intensity were directly observed. Data were analysed in the morning (0900-1100 h) and during the hottest time of day when cows were on pasture (1230-1430 h). The VT and RET showed similar patterns in relation to the CCI, suggesting that RET can be suitable for continuous monitoring of heat stress on pastures. In the morning, the cow's VT and RET did not relevantly react to the CCI. During the period 1230-1430 h, the cow's mean VT (mean vaginal temperature (VTMEAN); range: 37.7-40.3 °C) and mean RET (mean reticular temperature; range: 37.0-41.1 °C) were positively related to the mean CCI (mean comprehensive climate index) in this period (mean ± SD: 25.9 ± 5.71 °C). For cows with greater VTMEAN, an increased mean RR and decreased durations of walking, lying, feeding, and ruminating were found. These cows were also more likely to be in proximity to the water trough and to have small inter-individual distances. Changes in these traits seem to reflect behavioural adaptations to heat stress in a temperate climate and could be used to detect the heat stress in individual dairy cows on pastures.


Assuntos
Doenças dos Bovinos , Transtornos de Estresse por Calor , Feminino , Bovinos , Animais , Temperatura Corporal/fisiologia , Lactação/fisiologia , Temperatura , Temperatura Alta , Resposta ao Choque Térmico , Transtornos de Estresse por Calor/veterinária , Transtornos de Estresse por Calor/metabolismo , Água/metabolismo , Umidade , Leite/metabolismo , Doenças dos Bovinos/metabolismo
4.
J Dairy Sci ; 106(11): 8033-8046, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37641257

RESUMO

In the present experiment, 10 horned and 10 disbudded mid-lactating Brown Swiss cows were included in a crossover feeding trial with a hay or hay and concentrate diet. The effects of dietary neutral detergent fiber (NDF) content and horn status on thermoregulatory responses under thermoneutral and short-term heat stress conditions were studied, as both are considered to ease the cow's thermoregulation under an environmental heat load. Cows received either ad libitum hay and alfalfa pellets (85:15, C-, NDF content: 41.0%) or restricted amounts of hay and concentrate (70:30, C+, NDF content: 34.5%). The level of restriction applied with the C+ diet was determined from pre-experimental ad libitum intakes, ensuring that both diets provided the same intake of net energy for lactation (NEL). For data collection, cows were housed in respiration chambers for 5 d. The climatic conditions were 10°C and 60% relative humidity (RH), considered thermoneutral (TN) conditions (temperature-humidity index (THI): 52) for d 1 and 2, and 25°C and 70% RH, considered heat stress (HS) conditions (THI: 74), for d 4 and 5. On d 3, the temperature and RH were increased gradually. Compared with TN, HS conditions increased the water intake, skin temperature, respiration and heart rates, and endogenous heat production. They did not affect body temperature, feed intake, or milk production. Lowering dietary fiber content via concentrate supplementation lowered methane and increased carbon dioxide production. It did not mitigate physiological responses to HS. Although the responses of horned and disbudded cows were generally similar, the slower respiration rates of horned cows under HS conditions indicate a possible, albeit minor, role of the horn in thermoregulation. In conclusion, future investigations on nutritional strategies must be conducted to mitigate mild heat stress.

5.
Eur J Cancer ; 190: 112941, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37482012

RESUMO

AIM: ImmunoCobiVem investigated whether a planned switch to atezolizumab after achieving tumour control during run-in with vemurafenib + cobimetinib improves progression-free survival (PFS) and overall survival (OS) compared to continuous targeted therapy (TT) in patients with previously untreated advanced BRAFV600-mutated melanoma. METHODS: In this multicenter phase 2 study, patients received vemurafenib plus cobimetinib. After 3months, patients without progressive disease (PD) were randomly assigned (1:1) to continue vemurafenib + cobimetinib (Arm A) or switch to atezolizumab (Arm B) until first documented PD (PD1). Primary outcome was PFS1 (time from start of run-in until PD1 or death). OS and safety were also assessed. RESULTS: Of 185 patients enroled between November 2016 and December 2019, 135 were randomly assigned after the run-in period (Arm A, n = 69; Arm B, n = 66). Median PFS1 was significantly longer in Arm A versus Arm B (13.9 versus 5.9months; hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.37-0.84; PStratified=0.001). Median OS was not reached in either arm (HR 1.22; 95%CI, 0.69-2.16; PStratified=0.389); 2-year OS was higher in Arm B versus Arm A (67%; 95%CI, 53-78 versus 58%; 95%CI, 45-70). Grade 3/4 AEs occurred in 55% of patients in Arm A and 64% in Arm B; treatment-related AEs led to discontinuation of any drug in 7% and 9% of patients, respectively. CONCLUSION: In patients with BRAFV600-mutated advanced melanoma who achieve tumour control with TT, early switch at 3months to atezolizumab led to rapid loss of tumour control but provided a numerical OS benefit at 2years compared with continued TT.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Vemurafenib , Proteínas Proto-Oncogênicas B-raf/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Melanoma/tratamento farmacológico , Melanoma/genética , Mutação , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética
6.
J Dairy Sci ; 106(10): 6816-6833, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37500448

RESUMO

This study investigated the effects of acacia (extract of Acacia mearnsii) and sainfoin (Onobrychis viciifolia) as condensed tannin (CT)-rich sources on ruminal and manure methane (CH4) emissions in comparison with non-CT silages characterized by different contents of the cell wall and water-soluble carbohydrates. In a 3 × 6 incomplete Latin square design, 30 Holstein cows (63 ± 23 d in milk; mean ± SD; 33.8 ± 7.6 kg of milk per day, body weight 642 ± 81 kg) were provided with ad libitum access to 1 of 6 total mixed rations comprising 790 g of silage and 210 g of concentrate per kilogram of dry matter (DM). The silages were either rich in sainfoin [neutral detergent fiber (NDF): 349 g/kg of DM], perennial ryegrass (NDF: 420 g/kg of DM), or red clover (NDF: 357 g/kg of DM). Each silage was supplemented with 20 g/kg (of total diet DM) of acacia or straw meal. Feed intake and milk yield were recorded daily. Milk composition and ruminal fluid characteristics and microbiota were analyzed. The individual ruminal CH4 production was determined using the GreenFeed system, and CH4 emissions from the manure of cows fed the same diets were measured in a parallel experiment over 30 d at 25°C using a dynamic flux chamber. The CT sources did not reduce CH4 yield or emission intensity. Acacia reduced milk production (from 26.3 to 23.2 kg/d) and DM intake (from 19.7 to 16.7 kg/d) when supplemented with ryegrass, and both CT sources reduced the milk protein content and yield. Acacia supplementation and ryegrass silage reduced the ruminal acetate:propionate ratio. Furthermore, during acacia treatment, the abundance of Methanobrevibacter archaea tended to be lower and that of Thermoplasmata was higher. Acacia reduced the CH4 emissions from manure for the ryegrass group by 17% but not for the sainfoin and clover groups. Feeding sainfoin silage resulted in the lowest manure-derived CH4 emissions (-47% compared with ryegrass). In conclusion, acacia reduced ruminal CH4 production by 10%, but not emission intensity, and the mitigation effect of sainfoin depended on the silage to which it was compared. Because mitigation was partially associated with animal productivity losses, careful evaluation is required before the implementation of tanniferous feeds in farm practice.


Assuntos
Acacia , Proantocianidinas , Feminino , Bovinos , Animais , Esterco , Lactação , Silagem/análise , Acacia/metabolismo , Metano/metabolismo , Digestão , Zea mays/metabolismo , Dieta/veterinária , Nutrientes , Rúmen/metabolismo
7.
Animal ; 17(5): 100785, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37060748

RESUMO

Because of the relevant effects of plant-derived polyphenols (PPs) on monogastrics and ruminants' nutrition, emissions and performance, an increasing number of in vivo and in vitro studies are being performed to better understand the mechanisms of action of polyphenols at both the ruminal and intestinal levels. The biological properties of these phenolic compounds strongly depend on their degradation, absorption and metabolism. The harmonised in vitro digestion method (INFOGEST) is one of the most reliable in vitro methods used to assess the bioaccessibility and or antioxidant activity of PP contained in different matrixes, as well as the interactions of PP and their degradation products with other feed ingredients. The effects of PP released from their matrix after in vitro digestion on different intestinal physiological parameters, such as epithelium integrity, can be further evaluated by the use of ex vivo models such as the Ussing chamber. This review aims to describe the combination of the INFOGEST method, coupled with the Ussing chamber as a valuable model for the digestion and subsequent effects and absorption of phenolic compounds in monogastrics and potentially in ruminants. The advances, challenges and limits of this approach are also discussed.


Assuntos
Digestão , Polifenóis , Animais , Polifenóis/farmacologia , Polifenóis/metabolismo , Fenóis/farmacologia , Intestinos , Antioxidantes/farmacologia , Antioxidantes/metabolismo
8.
Animal ; 17(3): 100718, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36827848

RESUMO

Even in temperate climate regions, an increase in ambient temperature and exposure to solar radiation can cause heat stress in lactating dairy cows. We hypothesised that grazing dairy cows exhibit short-term physiological changes due to increasing heat load under moderate climate conditions. Over two consecutive summers, 38 lactating Holstein dairy cows were studied in a full-time grazing system. Data were collected in 10 experimental periods of up to three consecutive days with a moderate comprehensive climate index (CCI). The individual animals' vaginal temperature (VT), heart rate, and locomotor activity data were automatically monitored with sensors. Blood samples and proportional whole milk samples were collected at afternoon milking. The concentrations of beta-hydroxybutyrate, glucose, non-esterified fatty acids, urea nitrogen, plasma thyroxine and triiodothyronine were analysed in blood plasma, and fat, protein, lactose, urea nitrogen, cortisol, Na+, K+, and Cl- concentrations were analysed in milk. The daily distribution of VT recordings greater than 39 °C showed a circadian rhythm with a proportion of recordings of 2% and lower during the night and a percentage of 10% or higher in the afternoon. The cows' maximal daily vaginal temperature (VTMAX) between 0830 and 1430 h was positively related to the mean daily CCI in the same time period (CCIMEAN; mean and SD 23.6 ± 5.4 °C). Cows with greater VTMAX had an increased mean heart rate, plasma glucose and milk cortisol concentrations and decreased concentrations of plasma thyroxine and triiodothyronine. The concentration of Na+ in milk was lower, and the concentration of K+ in milk tended to be higher in cows with increased VTMAX. For beta-hydroxybutyrate, non-esterified fatty acids and urea nitrogen concentrations in plasma and fat and lactose concentrations in milk no relationships were found in terms of increasing VT. For milk urea nitrogen and protein concentrations, the proportion of total variance explained by inter-individual or -period variance was high. In conclusion, changes observed in milk and blood likely reflected short-term physiological responses to moderate heat stress. In particular, milk cortisol and Na+ may be useful traits for timely monitoring of heat stress in individual cows because their inter-individual variances were relatively small and samples can be collected non-invasively.


Assuntos
Lactação , Proteínas do Leite , Feminino , Bovinos , Animais , Lactação/fisiologia , Proteínas do Leite/análise , Tiroxina , Tri-Iodotironina , Ácido 3-Hidroxibutírico , Lactose/metabolismo , Hidrocortisona/metabolismo , Temperatura Alta , Leite/metabolismo , Resposta ao Choque Térmico/fisiologia , Ácidos Graxos não Esterificados , Ureia/metabolismo , Dieta/veterinária
9.
Geophys Res Lett ; 49(3): e2021GL096069, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35859568

RESUMO

Water storage plays an important role in mitigating heat and flooding in urban areas. Assessment of the water storage capacity of cities remains challenging due to the inherent heterogeneity of the urban surface. Traditionally, effective storage has been estimated from runoff. Here, we present a novel approach to estimate effective water storage capacity from recession rates of observed evaporation during precipitation-free periods. We test this approach for cities at neighborhood scale with eddy-covariance based latent heat flux observations from 14 contrasting sites with different local climate zones, vegetation cover and characteristics, and climates. Based on analysis of 583 drydowns, we find storage capacities to vary between 1.3 and 28.4 mm, corresponding to e-folding timescales of 1.8-20.1 days. This makes the urban storage capacity at least five times smaller than all the observed values for natural ecosystems, reflecting an evaporation regime characterized by extreme water limitation.

11.
Eur Phys J C Part Fields ; 82(2): 121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35210938

RESUMO

We present the novel implementation of a non-differentiable metric approximation and a corresponding loss-scheduling aimed at the search for new particles of unknown mass in high energy physics experiments. We call the loss-scheduling, based on the minimisation of a figure-of-merit related function typical of particle physics, a Punzi-loss function, and the neural network that utilises this loss function a Punzi-net. We show that the Punzi-net outperforms standard multivariate analysis techniques and generalises well to mass hypotheses for which it was not trained. This is achieved by training a single classifier that provides a coherent and optimal classification of all signal hypotheses over the whole search space. Our result constitutes a complementary approach to fully differentiable analyses in particle physics. We implemented this work using PyTorch and provide users full access to a public repository containing all the codes and a training example.

12.
Dermatologie (Heidelb) ; 73(9): 722-726, 2022 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34985572

RESUMO

We report the case of a 48-year-old multimorbid man who received allogeneic bone marrow transplantation 26 years ago for chronic myeloid leukemia. For 24 years, the patient suffered from sclerodermiform chronic graft-versus-host disease (GVHD) of the skin and lung with partial lung resection and immunosuppressive therapy. Recurrent ulcerations developed on the lower legs at the sites affected by cutaneous GVHD. The patient presented to our clinic with an ulcer progressive in size with resistance to previous therapy. Histologically, squamous cell carcinoma was found. Magnetic resonance imaging showed bone involvement and cutaneous in-transit metastasis, and computed tomography revealed a metastasis in the sacrum. Before therapy was initiated, the patient died suddenly as a result of his previous illnesses. The development of cutaneous GVHD is common in patients with allogeneic stem cell transplantation. The risk for the development of squamous cell carcinoma is increased. Patients should be under close dermatologic surveillance. If squamous cell carcinoma is suspected in pre-existing GVHD, biopsy should be performed promptly to reduce the risk of metastasis.


Assuntos
Carcinoma de Células Escamosas , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Dermatopatias , Transplante de Medula Óssea/efeitos adversos , Carcinoma de Células Escamosas/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Dermatopatias/etiologia , Úlcera/etiologia
13.
Environ Res Lett ; 17(4): 044041, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37600746

RESUMO

Recent advances in citizen weather station (CWS) networks, with data accessible via crowd-sourcing, provide relevant climatic information to urban scientists and decision makers. In particular, CWS can provide long-term measurements of urban heat and valuable information on spatio-temporal heterogeneity related to horizontal heat advection. In this study, we make the first compilation of a quasi-climatologic dataset covering six years (2015-2020) of hourly near-surface air temperature measurements obtained via 1560 suitable CWS in a domain covering south-east England and Greater London. We investigated the spatio-temporal distribution of urban heat and the influences of local environments on climate, captured by CWS through the scope of Local Climate Zones (LCZ)-a land-use land-cover classification specifically designed for urban climate studies. We further calculate, for the first time, the amount of advected heat captured by CWS located in Greater London and the wider south east England region. We find that London is on average warmer by about 1.0 ∘C-1.5 ∘C than the rest of south-east England. Characteristics of the southern coastal climate are also captured in the analysis. We find that on average, urban heat advection (UHA) contributes to 0.22 ± 0.96 ∘C of the total urban heat in Greater London. Certain areas, mostly in the centre of London are deprived of urban heat through advection since heat is transferred more to downwind suburban areas. UHA can positively contribute to urban heat by up to 1.57 ∘C, on average and negatively by down to -1.21 ∘C. Our results also show an important degree of inter- and intra-LCZ variability in UHA, calling for more research in the future. Nevertheless, we already find that UHA can impact green areas and reduce their cooling benefit. Such outcomes show the added value of CWS when considering future urban design.

14.
Br J Dermatol ; 186(1): 69-77, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34289097

RESUMO

BACKGROUND: The German programme for skin cancer screening was established in 2008 with the aim of reducing skin cancer mortality. However, the effectiveness and risk-benefit ratio of the programme remain unclear. OBJECTIVES: To compare the mortality rates of patients with melanoma who participate in a screening programme to those who do not. METHODS: A retrospective cohort study, based on pseudonymized health insurance data of 1 431 327 individuals from Saxony, Germany, was conducted for the period 2010-2016. Patients with prevalent and incident melanoma were defined based on diagnosis, medical procedures and prescriptions. Patients who underwent screening and had a first diagnosis of melanoma within 2 years of screening were assigned to the intervention group. Relative survival and Cox regression were used to assess potential differences in mortality. RESULTS: We identified 4552 individuals with prevalent and 2475 individuals with incident melanoma. The percentage of screening participants (n = 1801) who had locoregional (4·2% vs. 13·5%) and/or distant metastases (4·3% vs. 8·0%), or who were treated with systemic anticancer therapies (11·6% vs. 21·8%) was lower vs. nonparticipants (n = 674). Screening participants had significantly better survival rates. The unadjusted Cox model gave a hazard ratio (HR) of 0·37 [95% confidence interval (CI) 0·30-0·46]. After adjusting for named confounders, the effect remained (HR 0·62, 95% CI 0·48-0·80). CONCLUSIONS: Patients who participated in the screening programme had lower mortality than those who had not undergone screening. However, these findings may result from a healthy screen bias and/or overdiagnosis associated with screening, and not from the screening itself.


Assuntos
Melanoma , Neoplasias Cutâneas , Estudos de Coortes , Detecção Precoce de Câncer , Humanos , Programas de Rastreamento/métodos , Melanoma/patologia , Estudos Retrospectivos
15.
Br J Dermatol ; 185(6): 1186-1199, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34185311

RESUMO

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin cancer arising from the eccrine sweat glands. Due to the lack of effective therapies, metastasis is associated with a high mortality rate. OBJECTIVES: To investigate the drivers of EPC progression. METHODS: We carried out genomic and transcriptomic profiling of metastatic EPC (mEPC), validation of the observed alterations in an EPC patient-derived cell line, confirmation of relevant observations in a large patient cohort of 30 tumour tissues, and successful treatment of a patient with mEPC under the identified treatment regimens. RESULTS: mEPC was characterized by a high tumour mutational burden (TMB) with an ultraviolet signature, widespread copy number alterations and gene expression changes that affected cancer-relevant cellular processes such as cell cycle regulation and proliferation, including a pathogenic TP53 (tumour protein 53) mutation, a copy number deletion in the CDKN2A (cyclin dependent kinase inhibitor 2A) region and a CTNND1/PAK1 [catenin delta 1/p21 (RAC1) activated kinase 1] gene fusion. The overexpression of EGFR (epidermal growth factor receptor), PAK1 and MAP2K1 (mitogen-activated protein kinase kinase 1; also known as MEK1) genes translated into strong protein expression and respective pathway activation in the tumour tissue. Furthermore, a patient-derived cell line was sensitive to EGFR and MEK inhibition, confirming the functional relevance of the pathway activation. Immunohistochemistry analyses in a large patient cohort showed the relevance of the observed changes to the pathogenesis of EPC. Our results indicate that mEPC should respond to immune or kinase inhibitor therapy. Indeed, the advanced disease of our index patient was controlled by EGFR-directed therapy and immune checkpoint inhibition for more than 2 years. CONCLUSIONS: Molecular profiling demonstrated high TMB and EGFR/MAPK pathway activation to be novel therapeutic targets in mEPC.


Assuntos
Porocarcinoma Écrino , Receptores ErbB , Sistema de Sinalização das MAP Quinases , Neoplasias das Glândulas Sudoríparas , Porocarcinoma Écrino/genética , Receptores ErbB/genética , Humanos , Terapia de Alvo Molecular , Mutação , Neoplasias das Glândulas Sudoríparas/tratamento farmacológico , Neoplasias das Glândulas Sudoríparas/genética
16.
J Eur Acad Dermatol Venereol ; 35(8): 1678-1685, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33931910

RESUMO

BACKGROUND: Basal cell carcinoma (BCC) can arise by the uncontrolled proliferation of cells from multiple epidermal compartments due to aberrant activation of the Hedgehog (Hh) signalling pathway. Vismodegib, a small-molecule inhibitor of this pathway, is approved for treatment of patients with locally advanced (la) BCC inappropriate for surgery or radiotherapy or patients with symptomatic metastatic (m) BCC. OBJECTIVES: The aim of this non-interventional study was to assess effectiveness with a special focus on duration of response (DOR), safety and utilization of vismodegib for treatment of laBCC in daily practice in Germany. METHODS: This non-interventional study (NIS) observed treatment of laBCC with vismodegib according to the German label in clinical practice. All available patients who had received at least one dose of vismodegib between commercial availability of vismodegib in Germany (02 August 2013) and 3 years before end of study (31 March 2016) could be included and were documented retrospectively and/or prospectively for up to 3 years. Primary effectiveness variable was DOR. Assessment of tumour response was carried out by the treating physicians. Exploratory variables included utilization of vismodegib, decision makers for therapy and method of tumour response evaluation. All statistical analyses were descriptive. RESULTS: Between September 2015 and March 2019, 66 patients were observed at 26 German centres. The objective response rate (ORR) was 74.2% and the disease control rate (DCR) was 90.9%. The median DOR was 15.9 months (95% CI: 9.2; 25.7; n = 49 patients with response). The median progression-free survival (PFS) was 19.1 months and the median time to response (TTR) 2.7 months. A total of 340 adverse events were reported in 63 (95.5%) patients; no new safety signals were identified. CONCLUSIONS: The NIS NIELS shows effectiveness and safety of vismodegib in patients with laBCC. It confirms the transferability of the results of the pivotal trial into routine clinical practice.


Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Basocelular/tratamento farmacológico , Alemanha , Proteínas Hedgehog , Humanos , Piridinas , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico
20.
Animal ; 15(2): 100110, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33573985

RESUMO

Sainfoin is a protein-rich legume with an ideal amino acid profile and therefore could partly replace soybeans in the diets of growing pigs. However, sainfoin also contains a non-negligible amount of condensed tannins (CTs), which can act as antinutritional factors. Bioactive plant compounds, like hydrolysable tannins, have been suggested to be suitable in entire male (EM) production, as they impair the development of accessory sex glands and, by that, reduce boar taint compound levels without negatively impacting growth. It is unknown whether, similar to hydrolysable tannins, CTs from sainfoin reduce the incidence of boar taint without impacting growth performance, carcass traits, and meat quality. For the experiment, 48 Swiss Large White EM were assigned within litter to one of four grower (25-60 kg BW) and finisher (60-105 kg BW) diets supplemented with 0 (T0), 5 (T5), 10 (T10), and 15% (T15) sainfoin meal, respectively. The four diets were designed to be isocaloric and isoproteic. Increasing the dietary sainfoin level had no negative effect on growth performance or the carcass characteristics. Despite leading to a similar feed intake between the treatment groups, increasing the dietary sainfoin levels tended (P ≤ 0.08) to reduce the number of feeder visits but increased the time spent at the feeder as well as the feed intake per visit during the finisher period. By increasing sainfoin intake, the levels of C18:3n-3 and long-chain homologs linearly increased (P < 0.01) in the backfat and intramuscular fat (IMF), whereas in the backfat, but not the IMF, the 18:2n-6 levels decreased (P < 0.01). The latter triggered a greater (P < 0.01) desaturation rate (C18:1n-9/C18:0) of the saturated fatty acids, resulting in a greater (P < 0.01) proportion of monounsaturated fatty acid. Apart from a linear decrease (P = 0.02) in the androstenone levels in the longissimus thoracis (LT), increasing the sainfoin intake had no effect on the level of boar taint in the LT and backfat. As determined by the elevated correlation coefficient, skatole and indole levels, but not androstenone levels, in the adipose tissue seem to be reliable proxies for their respective levels in LT and, therefore, in pork. In conclusion, sainfoin is a suitable homegrown protein source for grower finisher pigs and can be included at up to 15% in the diet to replace 7% of soybean in a diet without producing any noteworthy effects on growth, whereas the impact of CTs on boar taint was limited.


Assuntos
Ração Animal , Proantocianidinas , Ração Animal/análise , Animais , Composição Corporal , Dieta/veterinária , Masculino , Carne , Suínos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...