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Brown Swiss (BS) cows have greater urea concentrations in milk and blood compared with Holstein (HO) cows. We tested the hypothesis that BS and HO cows differ in kidney function and nitrogen excretion. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. To test the glomerular filtration rate (GFR) and urea excretion, concentrations of creatinine and urea were measured in serum, urine, and saliva. As an additional marker to estimate GFR, we determined symmetric dimethylarginine (SDMA) in serum. Feces were analyzed for dry matter content and nitrogen concentration. Data on milk urea and protein concentrations, and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test at P < 0.05. Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows (P < 0.01): 5.46 ± 0.19 vs 4.72 ± 0.13 mmol/L (urea), 105.96 ± 2.23 vs 93.07 ± 1.50 mmol/l (creatinine), and 16.78 ± 0.69 vs 13.39 ± 0.44 µg/dL (SDMA). We observed a greater urea concentration in BS cows (25.8 ± 0.7 vs 21.8 ± 0.7 mg/dL) and protein content in milk (3.70 ± 0.08 vs 3.45 ± 0.07%) than in HO cows (P < 0.01). Urea and creatinine concentrations in urine and saliva did not differ among breeds. No differences between BS and HO were observed for milk yield, fecal DM, and fecal nitrogen content. Dry matter intake and body weight were similar in BS and HO cows (P > 0.05). Despite greater urea, creatinine, and SDMA concentrations in blood as well as a higher milk urea content in BS compared with HO, respective concentrations in urine did not differ between breeds. In conclusion, our results demonstrate a lower renal GFR in BS compared with HO cows, thereby contributing to the greater plasma urea concentration in BS cows. However, estimation of nitrogen excretion via milk, urine, and feces does not entirely reflect nitrogen turnover within the animal.
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PURPOSE: The outcomes of five fraction stereotactic radiotherapy (hfSRT) following brain metastasectomy were evaluated and compared with published series. METHODS: 30 Gy in 5 fractions HfSRT prescribed to the surgical cavity was reduced to 25 Gy if the volume of 'brain-GTV' receiving 20 Gy exceeded 20 cm3. Endpoints were local recurrence, nodular leptomeningeal recurrence, new brain metastases and radionecrosis. The literature was searched for reports of clinical and dosimetric outcomes following postoperative hfSRT in 3-5 fractions. RESULTS: 39 patients with 40 surgical cavities were analyzed. Cavity local control rate at 1 year was 33/40 (82.5%). 3 local failures followed 30 Gy/5 fractions and 4 with 25 Gy/5 fractions. The incidence of leptomeningeal disease (LMD) was 7/40 (17.5%). No grade 3-4 toxicities, particularly no radionecrosis, were reported. The incidence of distant brain metastases was 15/40 (37.5%). The median overall survival was 15 months. Across 13 published series, the weighted mean local control was 83.1% (adjusted for sample size), the mean incidence of LMD was 14.9% (7-34%) and the mean rate of radionecrosis was 10.3% (0-20.6%). CONCLUSION: Postoperative hfSRT can be delivered with 25-30 Gy in 5 fractions with efficacy in excess of 82% and no significant toxicity when the dose to 'brain-GTV' does not exceed 20 cm3.
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Neoplasias Encefálicas , Metastasectomía , Traumatismos por Radiación , Radiocirugia , Encéfalo , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Humanos , Neoplasias Meníngeas , Hipofraccionamiento de la Dosis de Radiación , Radiocirugia/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Newborn ungulates depend on the timely supply of colostrum containing sufficient immunoglobulins to obtain passive immunity against disease. Brix refractometry enables a rapid on-farm estimation of colostrum quality and has been intensively studied in bovines. However, the suitability of Brix refractometers for assessing colostrum quality in goats and ewes has been scarcely evaluated. The present study compared bovine, caprine, and ovine colostrum quality estimation using an optical Brix refractometer. In addition, between-species variations in the relationships between Brix values and colostrum constituents (IgG, fat, protein, and lactose) and the accuracy of Brix refractometry at different cutoff values were evaluated by a receiver operating characteristic curve analysis. We measured the Brix value and contents of IgG, fat, protein, and lactose in 324 colostrum samples (108 cows, 116 does, and 100 ewes). Thresholds for classification of good colostrum quality (as determined by ELISA) were set at 50 mg IgG/mL in cows and 20 mg/mL in does and ewes. Bovine colostrum showed the greatest IgG concentrations compared with caprine and ovine colostrum. Fat and protein content was higher in sheep colostrum compared with the other species, whereas the highest lactose concentrations were detected in goat colostrum. Brix values ranged from 11.4 to 34.6% (22.1 ± 4.2%; mean ± standard deviation), 15.4 to 40.0% (28.5 ± 6.8%), and 8.8 to 39.8% (21.6 ± 5.3%) in bovine, ovine, and caprine colostrum, respectively. In all 3 species, Brix was highly correlated with IgG and protein concentrations (cows, r = 0.83 and 0.98; goats, r = 0.83 and 0.89; sheep, r = 0.75 and 0.87). Optimal cutoff points for greatest accuracy of Brix measurements were 19.3% Brix in cows [with 87.1% sensitivity (Se) and 100% specificity (Sp)], 20.7% Brix in does (with 53.5% Se and 100% Sp), and 26.5% Brix in ewes (with 75% Se and 91.3% Sp). In conclusion, Brix refractometry is an acceptable tool for on-farm estimations of colostrum quality in does and ewes despite distinct between-species variations in colostrum composition.
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Bovinos , Calostro/química , Cabras , Refractometría/veterinaria , Ovinos , Animales , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Cabras/inmunología , Lactosa , Embarazo , Curva ROC , Ovinos/inmunologíaRESUMEN
First colostrum yield and constituents as well as milk yield during established lactation vary considerably among mammary quarters in dairy cows. However, data on the development of milk yield, IgG concentration, and their distribution per quarter within cows during the first milkings after calving are scarce. We analyzed milk production and IgG concentration at the individual quarter level in 29 multiparous Holstein cows during the first 5 milkings after calving. Cow- and calf-related factors (time interval between calving and first milking, parity number, previous lactation yield, gestation length, dry period length, sex, and birth weight of the calf) potentially affecting first colostrum quality and quantity were assessed. Milking of first colostrum was carried out between 30 and 180 min after parturition. Further milkings were performed twice daily. Quarter milk yield varied between 0.1 and 5.5 kg at the first milking and between 1.4 and 5.1 kg at the fifth milking relative to parturition. Quarter IgG concentration ranged between 18.8 and 106.0 mg/mL at the first milking and between 0.8 and 46.1 mg/mL at the fifth milking. Distribution of milk yield and IgG concentration among quarters was not entirely repeatable during the first 5 successive milkings after parturition; that is, the ranking of quarters changed (intraclass correlation coefficients for quarter milk yield and IgG concentration: 0.64 and 0.79, respectively). The average hourly milk production increased in all quarters, ranging from 0.02 to 0.26 kg/h between the first 2 milkings up to 0.11 to 0.45 kg/h between the fourth and fifth milkings. First colostrum yield was not affected by any of the evaluated cow- and calf-related factors. Quarter colostrum IgG concentration was higher in cows with a higher previous lactation yield, whereas a lower colostrum IgG content was observed in cows with a longer gestation period and consequently heavier calves. In conclusion, milk yield and IgG concentration of individual quarters varied considerably, and their distribution among quarters within cows was moderately repeatable in consecutive milkings and changed partially over time. The decline of IgG concentration was independent of the concomitant increase in milk secretion, with changes occurring at different rates in individual quarters. Our results confirm the independence of the single mammary quarters at the onset of lactation despite an identical exposure to endocrine stimuli.
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Bovinos/fisiología , Calostro/fisiología , Inmunoglobulina G/química , Leche/fisiología , Parto/fisiología , Animales , Calostro/química , Femenino , Lactancia , Paridad , EmbarazoRESUMEN
Colostrum represents the sole source to acquire humoral immunity and is an important energy source for newborn lambs and goat kids. However, colostrum composition (i.e., the contents of IgG, fat, protein, and lactose) is affected by various factors such as parity and litter size and, potentially, by breed. In the present study, we examined the colostrum composition of different goat and sheep breeds raised for milk and meat production in Switzerland and Germany. Ten goat breeds (Anglo-Nubian, Appenzell, Boer, Bunte Deutsche Edelziege, Chamois-colored, Grisons Striped, Peacock, Saanen, Toggenburg, and Valais Blackneck) and 10 sheep breeds (Brown-Headed Meat, East Friesian Milk, German Blackheaded Mutton, Gray Horned Heath, Lacaune Dairy, Merino Land, Swiss Black-Brown Mountain, Swiss Charollais, Swiss White Alpine, and Valais Blacknose) were involved in this study. First colostrum samples were obtained from ewes (n = 100) and goats (n = 116) between 10 and 390 min after parturition and analyzed for total IgG, fat, protein, and lactose contents. Colostral IgG concentrations varied between 4.8 and 75.0 mg/mL in goats, and between 6.2 and 65.4 mg/mL in ewes, and the time interval between milking and parturition did not affect colostral IgG concentrations. In goats, the highest IgG concentrations were found in Boer (meat-type; 61.0 ± 10.3 mg/mL; mean ± SD) and the lowest concentrations were observed in Bunte Deutsche Edelziege (milk-type; 26.5 ± 12.5 mg/mL). In sheep, East Friesian Milk and Lacaune Dairy showed the lowest colostral IgG concentrations (17.9 ± 7.3 and 20.2 ± 8.0 mg/mL, respectively), and the highest values were observed in the Merino Land breed (44.2 ± 15.7 mg/mL). The lowest fat and protein concentrations and concomitantly highest lactose concentrations were observed in colostrum of East Friesian Milk and Lacaune Dairy sheep. Parity number did not affect colostrum composition in sheep or goats. In contrast, colostral fat content was higher in ewes bearing twins and triplets than in those carrying singletons. Increasing litter size tended to be associated with higher protein and lower lactose concentrations in ovine (i.e., singletons vs. twins vs. triplets) and caprine colostrum (i.e., singletons vs. twins), whereas colostral IgG concentrations were not affected by litter size. In conclusion, IgG and concentrations of other colostrum constituents showed a wide range in goats and ewes and were mainly affected by the type of breed.
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Calostro/química , Cabras/inmunología , Inmunoglobulina G/análisis , Leche/metabolismo , Ovinos/inmunología , Animales , Calostro/inmunología , Ácidos Grasos/análisis , Femenino , Alemania , Lactosa/análisis , Tamaño de la Camada , Paridad , Parto , Embarazo , Proteínas/análisis , Especificidad de la Especie , SuizaRESUMEN
After parturition, the start of copious milk production in dairy cows requires the closure of tight junctions (TJ) to form the blood-milk barrier and prevent paracellular transfer of blood constituents into milk [e.g., lactate dehydrogenase (LDH) and serum albumin (SA)] and vice versa [e.g., appearance of α-lactalbumin (α-LA) in blood]. Serotonin (5-HT) has been demonstrated to alter tight junction permeability in the mammary gland. The present study investigated individual differences of TJ permeability of mammary epithelium at the beginning of lactation in relation to circulating 5-HT in dairy cows. Blood and milk samples were obtained from 11 multiparous Holstein dairy cows for the first time at 4 h after parturition, at the following 5 milkings, and at the evening milkings on d 5, 8, 10, and 14 of lactation. Retrospectively, cows were split into 2 groups according to their calculated areas under the curve of serum 5-HT during the entire experimental period: a high-serum 5-HT (HSS) group (5 cows) and a low-serum 5-HT (LSS) group (6 cows). The areas under the curve of serum 5-HT concentrations over the 324-h experimental period were 62 ± 2 × 103 ng/mL in HSS and 25 ± 5 × 103 ng/mL in LSS. Plasma α-LA concentration was greater in LSS than in HSS cows at the first milking, but no difference between groups was found from the second to sixth milking. Yield of α-LA in milk was lower in HSS than in LSS during the first 6 milkings postpartum, especially in colostrum. Concentrations of α-LA, IgG1, and IgG2 in milk did not differ between groups during the entire experiment except for higher IgG observed in LSS than in HSS at the second milking and for higher IgG2 found in HSS compared with LSS on d 5. In contrast, SA concentrations and LDH activity in milk were lower in LSS compared with HSS cows during the first 6 milkings postpartum, particularly in colostrum. Milk somatic cell count was higher in HSS than in LSS throughout the study. Higher circulating 5-HT concentrations were associated with an increased transfer of the paracellularly transported SA, LDH, and somatic cell count, especially at the first milking, suggesting that 5-HT affects TJ permeability during closure of the blood-milk barrier at the onset of lactation. Furthermore, higher serum 5-HT concentrations were associated with a lower α-LA yield in milk. A consistent relationship with serum 5-HT concentrations was neither observed for the transfer of IgG2 nor the primarily transcellular transport of IgG1 during the first milkings after parturition.
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Bovinos/sangre , Serotonina/sangre , Uniones Estrechas/metabolismo , Animales , Bovinos/fisiología , Parto Obstétrico , Femenino , Inmunoglobulina G/sangre , Lactalbúmina/sangre , Lactancia/sangre , Leche/metabolismo , Parto , Permeabilidad , Periodo Posparto , Embarazo , Estudios Retrospectivos , Albúmina Sérica/metabolismoRESUMEN
Serotonin (5-hydroxytryptamine, 5-HT) affects many physiological functions because it is involved in glucose and lipid metabolism, calcium homeostasis, and regulation of lactation in dairy cows. This study aimed to examine physiological differences in serum 5-HT concentrations (high vs. low) and their association with metabolic status and milk production at the onset of lactation. Twelve multiparous Holstein dairy cows were milked within 4 h of calving, and blood and milk samples were collected at the first 6 subsequent milkings after parturition and at the evening milkings on d 5, 8, 10, and 14. Cows were retrospectively divided into 2 groups (6 cows/group): low serum 5-HT (LSS) and high serum 5-HT (HSS) according to their calculated areas under the curve (AUC) for serum 5-HT for the entire experimental period (cut-off: 46,000 ng/mL × 324 h). Concentrations of 5-HT, free fatty acids (FFA), ß-hydroxybutyrate (BHB), glucose, calcium, and IGF-1 were measured in blood. Milk was analyzed for fat, protein, lactose, and 5-HT concentrations. Milk yield was recorded at each milking and energy-corrected milk yield was calculated. Serum 5-HT concentrations were higher in HSS than in LSS [AUC (ng/mL × 324 h): 57,830 ± 4,810 vs. 25,005 ± 5,930]. The amount of energy-corrected milk was lower in HSS than in LSS. The HSS group produced less colostrum and had decreased milk yield, specifically during the first 6 milkings. Concentrations of FFA, BHB, and glucose in plasma did not differ between groups. Concentrations of IGF-1 in serum were elevated in HSS compared with LSS throughout the experiment. Total circulating calcium concentrations in serum tended to be higher in HSS than in LSS. Milk fat and protein yields were decreased in HSS compared with LSS. Milk 5-HT decreased overall during the experimental period, with LSS maintaining higher 5-HT concentrations than HSS until d 14 of lactation. In conclusion, cows with high serum 5-HT concentrations showed a reduced metabolic load at the onset of lactation, concomitantly lower milk yield, and a reduced energy output via milk.
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Bovinos/sangre , Bovinos/fisiología , Serotonina/sangre , Ácido 3-Hidroxibutírico/sangre , Animales , Ácidos Grasos no Esterificados/sangre , Femenino , Factor I del Crecimiento Similar a la Insulina/metabolismo , Lactancia , Leche/metabolismo , Parto , Embarazo , Estudios RetrospectivosRESUMEN
Supplementing conjugated linoleic acid (CLA) is supposed to spare glucose due to the milk fat-depressing effect of the trans-10, cis-12 CLA isomer, and allows repartitioning nutrients despite an energy deficiency in early lactation. However, there is still a lack of knowledge in terms of the dynamic pattern of the glucose turnover in transition dairy cows. We hypothesized that dairy cows supplemented with CLA have an altered rate of glucose turnover and insulin sensitivity during early lactation. We conducted three consecutive hyperglycaemic clamps (HGC) in weeks -2, +2 and +4 relative to parturition in Holstein cows supplemented daily either with 70 g of lipid-encapsulated CLA (6.8 g trans-10, cis-12 and 6.6 g of the cis-9, trans-11 CLA isomer; CLA; n = 11) or with 56 g of control fat (CON; n = 11). From week -3 up to week +4 relative to parturition, milk yield and dry matter intake (DMI) were recorded daily, while body weight (BW) and milk composition were obtained once weekly. Blood samples were taken once weekly and every 30 min during the HGC. Plasma was analysed for concentrations of glucose, fatty acids (FFA), beta-hydroxybutyrate (BHB), insulin, triglycerides and cholesterol. The CLA supplementation did not affect performance and metabolic parameters except for BHB and cholesterol. Furthermore, insulin concentrations and insulin sensitivity were affected by treatment. During the HGC in early lactation, insulin response was lower and decrease in FFA and BHB greater compared with the HGC in week -2 although glucose target concentration achieved during the steady-state period was similar for all three HGC. Our findings in terms of insulin and cholesterol suggest that body reserves are preserved through CLA feeding without restraining animal's performance. Furthermore, CLA effects on cholesterol and triglyceride concentrations indicated beneficial effects on hepatic lipid export contributing to an improved efficiency of prevailing metabolites in circulation.
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Bovinos/fisiología , Glucosa/metabolismo , Hiperglucemia/veterinaria , Lactancia/fisiología , Ácidos Linoleicos Conjugados/farmacología , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Glucemia , Dieta/veterinaria , Suplementos Dietéticos , Femenino , Técnica de Clampeo de la Glucosa , Ácidos Linoleicos Conjugados/administración & dosificaciónRESUMEN
We propose a protocol for creating a fully entangled Greenberger-Horne-Zeilinger-type state of neutral atoms in spatially separated optical atomic clocks. In our scheme, local operations make use of the strong dipole-dipole interaction between Rydberg excitations, which give rise to fast and reliable quantum operations involving all atoms in the ensemble. The necessary entanglement between distant ensembles is mediated by single-photon quantum channels and collectively enhanced light-matter couplings. These techniques can be used to create the recently proposed quantum clock network based on neutral atom optical clocks. We specifically analyze a possible realization of this scheme using neutral Yb ensembles.
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We propose and analyze heralded quantum gates between qubits in optical cavities. They employ an auxiliary qubit to report if a successful gate occurred. In this manner, the errors, which would have corrupted a deterministic gate, are converted into a nonunity probability of success: once successful, the gate has a much higher fidelity than a similar deterministic gate. Specifically, we describe that a heralded, near-deterministic controlled phase gate (CZ gate) with the conditional error arbitrarily close to zero and the success probability that approaches unity as the cooperativity of the system, C, becomes large. Furthermore, we describe an extension to near-deterministic N-qubit Toffoli gate with a favorable error scaling. These gates can be directly employed in quantum repeater networks to facilitate near-ideal entanglement swapping, thus greatly speeding up the entanglement distribution.
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We propose and analyze a new approach based on quantum error correction (QEC) to improve quantum metrology in the presence of noise. We identify the conditions under which QEC allows one to improve the signal-to-noise ratio in quantum-limited measurements, and we demonstrate that it enables, in certain situations, Heisenberg-limited sensitivity. We discuss specific applications to nanoscale sensing using nitrogen-vacancy centers in diamond in which QEC can significantly improve the measurement sensitivity and bandwidth under realistic experimental conditions.
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We present a quantum-enhanced atomic clock protocol based on groups of sequentially larger Greenberger-Horne-Zeilinger (GHZ) states that achieves the best clock stability allowed by quantum theory up to a logarithmic correction. Importantly the protocol is designed to work under realistic conditions where the drift of the phase of the laser interrogating the atoms is the main source of decoherence. The simultaneous interrogation of the laser phase with a cascade of GHZ states realizes an incoherent version of the phase estimation algorithm that enables Heisenberg-limited operation while extending the coherent interrogation time beyond the laser noise limit. We compare and merge the new protocol with existing state of the art interrogation schemes, and identify the precise conditions under which entanglement provides an advantage for clock stabilization: it allows a significant gain in the stability for short averaging time.
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In dairy cows, milk yield increases rapidly after parturition until a peak at around wk 6 of lactation. However, the description of the shape of the lactation curve is commonly based on weekly average milk yields. For a more detailed analysis of the milk production curve from the very beginning of lactation including the colostral period and the effect of colostrum yield on further lactational performance, the first 10 milkings after parturition, daily milk yields from d 1 to 28 of lactation, and the cumulative milk production on d 100 to 305 of lactation were investigated in 17 primiparous and 39 multiparous cows milked twice daily. Milk yield at the first milking after parturition (colostrum) ranged from 1.3 to 20.7kg (Δ=19.4kg) in multiparous and from 1.8 to 10.9kg in primiparous animals (Δ=9.1kg). At the tenth milking, milk production ranged from 9.2 to 21.5kg (Δ=12.3kg) in multiparous and from 7.0 to 15.2kg (Δ=8.2kg) in primiparous animals. Immediately after parturition, daily milk production increased rapidly, but after approximately 1wk in lactation, the slope of the daily milk production curve flattened and continued more linear. A nonlinear regression equation was used to determine this timely change, which occurred earlier in primiparous (d 6.9±0.3) than in multiparous cows (d 8.2±0.2). The correlation between the amount of first colostrum and milk production during further lactation decreased already from 0.47 on d 5 to 0.32 on d 14. In multiparous cows, the correlation between total milk production of the previous 305d standard lactation and the amount of first colostrum was not significant (correlation=0.29), whereas the correlation with the daily production increased from 0.45 on d 5 to 0.69 on d 14. However, in primiparous animals, correlations between first-colostrum yield and daily milk yields up to d 28 of lactation were not significant, possibly due to the smaller sample size compared with multiparous animals. First-colostrum yield and cumulative milk production of 100, 200, and 305 lactation days were not significantly correlated in multiparous and primiparous cows. In conclusion, the milk production during the first few milkings is widely independent from the overall production level of a cow. Potentially, genetic selection toward lower milk yield during the very first days after parturition at a simultaneously high lactational performance may be a tool to ensure sufficient colostrum quality and to reduce the metabolic load around parturition.
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Bovinos/fisiología , Calostro/metabolismo , Lactancia , Leche/metabolismo , Animales , Industria Lechera , Femenino , Paridad , Parto , EmbarazoRESUMEN
The transition from the nonlactating to the lactating state represents a critical period for dairy cow lipid metabolism because body reserves have to be mobilized to meet the increasing energy requirements for the initiation of milk production. The purpose of this study was to provide a comprehensive overview on cholesterol homeostasis in transition dairy cows by assessing in parallel plasma, milk, and hepatic tissue for key factors of cholesterol metabolism, transport, and regulation. Blood samples and liver biopsies were taken from 50 multiparous Holstein dairy cows in wk 3 antepartum (a.p.), wk 1 postpartum (p.p.), wk 4 p.p., and wk 14 p.p. Milk sampling was performed in wk 1, 4, and 14 p.p. Blood and milk lipid concentrations [triglycerides (TG), cholesterol, and lipoproteins], enzyme activities (phospholipid transfer protein and lecithin:cholesterol acyltransferase) were analyzed using enzymatic assays. Hepatic gene expression patterns of 3-hydroxy-3-methylglutaryl-coenzyme A (HMGC) synthase 1 (HMGCS1) and HMGC reductase (HMGCR), sterol regulatory element-binding factor (SREBF)-1 and -2, microsomal triglyceride transfer protein (MTTP), ATP-binding cassette transporter (ABC) A1 and ABCG1, liver X receptor (LXR) α and peroxisome proliferator activated receptor (PPAR) α and γ were measured using quantitative RT-PCR. Plasma TG, cholesterol, and lipoprotein concentrations decreased from wk 3 a.p. to a minimum in wk 1 p.p., and then gradually increased until wk 14 p.p. Compared with wk 4 p.p., phospholipid transfer protein activity was increased in wk 1 p.p., whereas lecithin:cholesterol acyltransferase activity was lowest at this period. Total cholesterol concentration and mass, and cholesterol concentration in the milk fat fraction decreased from wk 1 p.p. to wk 4 p.p. Both total and milk fat cholesterol concentration were decreased in wk 4 p.p. compared with wk 1 and 14 p.p. The mRNA abundance of genes involved in cholesterol synthesis (SREBF-2, HMGCS1, and HMGCR) markedly increased from wk 3 a.p. to wk 1 p.p., whereas SREBF-1 was downregulated. The expression of ABCA1 increased from wk 3 a.p. to wk 1 p.p., whereas ABCG1 was increased in wk 14 p.p. compared with other time points. In conclusion, hepatic expression of genes involved in the biosynthesis of cholesterol as well as the ABCA1 transporter were upregulated at the onset of lactation, whereas plasma concentrations of total cholesterol, phospholipids, lipoprotein-cholesterol, and TG were at a minimum. Thus, at the gene expression level, the liver seems to react to the increased demand for cholesterol after parturition. Whether the low plasma cholesterol and TG levels are due to impaired hepatic export mechanisms or reflect an enhanced transfer of these compounds into the milk to provide essential nutrients for the newborn remains to be elucidated.
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Bovinos/fisiología , Lactancia , Metabolismo de los Lípidos , Hígado/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Ésteres del Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Femenino , Expresión Génica , Homeostasis , Hidroximetilglutaril-CoA Sintasa/genética , Hidroximetilglutaril-CoA Sintasa/metabolismo , Leche/química , PPAR alfa/genética , PPAR alfa/metabolismo , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Proteínas de Transferencia de Fosfolípidos/sangre , Periodo Posparto/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Triglicéridos/sangreRESUMEN
Colostrum formation and lactogenesis in the mammary gland and the timing of parturition are regulated by endocrine signals. Changes in progesterone (P4) and prolactin (PRL) are considered key events that inhibit colostrum formation, trigger parturition, and signal the onset of lactation. The goal of our study was to determine if colostrum yield and composition and immunoglobulin transfer are affected by prepartum milking relative to the decrease in P4, peak of PRL, or occurrence of parturition. Twenty-three multiparous cows were randomly assigned to 1 of 2 groups: (1) control with first milking at 4h postcalving (CON, n=11), and (2) treatment group with first milking approximately 1d before calving and second milking at 4h after parturition (APM, n=12). Colostrum yields were recorded and proportional samples were analyzed for immunoglobulin G (IgG) concentration. Blood plasma samples for the analyses of P4 and PRL were collected 3 times daily at 8-h intervals for 4d prepartum and again taken at 4h after parturition. Total colostrum mass of APM cows was higher than that of CON cows. Immunoglobulin G concentration and protein content did not differ between antepartum milking in APM cows and postpartum milking in CON cows. Colostrum IgG concentration and protein content in APM cows at the postpartum milking were lower compared with the IgG concentration established at the prepartum (APM) and postpartum milkings of CON cows. Immunoglobulin G mass did not differ in first and second colostrum collection in APM cows but was lower compared with that of CON cows. The sum of IgG mass in APM cows (prepartum + postpartum collections) did not differ from that of CON cows. Lactose and fat in milk (concentration and mass) increased from first to second milking in APM cows. Total mass of lactose and fat in APM cows (prepartum + postpartum collections) was greater compared with that of CON cows. The finding that the time of milking relative to parturition, P4 decrease, and PRL peak slightly affected yield and quality of colostrum emphasizes the complex interactions of numerous endocrine and morphological changes occurring during colostrogenesis and lactogenesis in dairy cows. The considerably rapid transfer of immunoglobulins into colostrum of prepartum-milked cows within a few hours leads to the hypothesis that the transfer of IgG can be very fast and-contrary to earlier findings-persist at least until parturition.
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Bovinos/fisiología , Calostro/química , Inmunoglobulina G/química , Periodo Periparto/fisiología , Progesterona/sangre , Prolactina/sangre , Animales , Transporte Biológico , Líquidos Corporales/química , Femenino , Lactancia/fisiología , Lactosa/metabolismo , Leche/química , Embarazo , Progesterona/metabolismo , Prolactina/metabolismoRESUMEN
BACKGROUND: The increased need for professional expertise in the domain of aging is accompanied by a lack of academic experts in geropsychology. MATERIALS AND METHODS: In order to analyze whether German universities, universities of applied science, and psychotherapy training institutions produce a sufficient number of graduates, two studies were conducted. RESULTS: A complete survey of all courses and modules (study 1) identified only 4 master courses (9.3 %) and no bachelor courses with a substantial focus on geropsychology. All gerontology courses hold a substantial focus on geropsychology; however, only 6 courses are available (5 master, 1 bachelor). In an online survey (study 2) 55 % of the N = 103 psychotherapy training institutions (58 % response rate) stated that they offer geropsychology classes, though only to an average extent of M = 12.7 lessons (â 2 % of the required theory lessons). CONCLUSION: There is urgent need to expand the number of graduates with academic education and clinical training in geropsychology and -psychotherapy.
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Competencia Clínica , Curriculum , Educación de Postgrado , Geriatría/educación , Psicología Clínica/educación , Psicoterapia/educación , Recolección de Datos , Alemania , HumanosRESUMEN
BACKGROUND: Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score. PATIENTS AND METHODS: Patients with treatment-naïve aRCC received NIVO 240 mg every 2 weeks plus CABO 40 mg once daily or SUN 50 mg for 4 weeks (6-week cycles), until disease progression/unacceptable toxicity (maximum NIVO treatment, 2 years). Primary endpoint was progression-free survival (PFS) per blinded independent central review (BICR). Secondary endpoints were overall survival (OS), objective response rate (ORR) per BICR, and safety and tolerability. RESULTS: Overall, 323 patients were randomised to NIVO + CABO and 328 to SUN. Median PFS was improved with NIVO + CABO versus SUN [16.6 versus 8.4 months; hazard ratio (HR) 0.59; 95% confidence interval (CI) 0.49-0.71]; median OS favoured NIVO + CABO versus SUN (49.5 versus 35.5 months; HR 0.70; 95% CI 0.56-0.87). ORR (95% CI) was higher with NIVO + CABO versus SUN [56% (50% to 62%) versus 28% (23% to 33%)]; 13% versus 5% of patients achieved complete response, and median duration of response was 22.1 months versus 16.1 months, respectively. PFS and OS favoured NIVO + CABO over SUN across intermediate, poor and intermediate/poor IMDC risk subgroups; higher ORR and complete response rates were seen with NIVO + CABO versus SUN regardless of IMDC risk subgroup. Any-grade (grade ≥3) treatment-related adverse events occurred in 97% (67%) versus 93% (55%) of patients treated with NIVO + CABO versus SUN. CONCLUSIONS: After extended follow-up, NIVO + CABO maintained survival and response benefits; safety remained consistent with previous follow-ups. These results continue to support NIVO + CABO as a first-line treatment for aRCC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03141177.
Asunto(s)
Anilidas , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Renales , Neoplasias Renales , Nivolumab , Piridinas , Sunitinib , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/mortalidad , Sunitinib/uso terapéutico , Sunitinib/farmacología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/mortalidad , Masculino , Anilidas/uso terapéutico , Anilidas/farmacología , Femenino , Persona de Mediana Edad , Nivolumab/uso terapéutico , Nivolumab/farmacología , Piridinas/uso terapéutico , Piridinas/farmacología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Adulto , Estudios de Seguimiento , Supervivencia sin ProgresiónRESUMEN
We propose a scheme for the deterministic generation of steady-state entanglement between the two nuclear spin ensembles in an electrically defined double quantum dot. Because of quantum interference in the collective coupling to the electronic degrees of freedom, the nuclear system is actively driven into a two-mode squeezedlike target state. The entanglement buildup is accompanied by a self-polarization of the nuclear spins towards large Overhauser field gradients. Moreover, the feedback between the electronic and nuclear dynamics leads to multistability and criticality in the steady-state solutions.
RESUMEN
Background and purpose: This study evaluated translational and rotational intra-fractional patient movement during spinal stereotactic body radiotherapy (SBRT) using 6D positioning based on 3D cone beam computerized tomography (CBCT) and stereoscopic kilovoltage imaging (ExacTrac). The aim was to determine whether additional intra-fractional image verification reduced intra-fractional motion without significantly prolonging treatment time, whilst maintaining acceptable imaging related dose. Materials and methods: A retrospective analysis of 38 patients with 41 primary tumour volumes treated with SBRT between September 2018 and May 2021 was performed. Three different image-guided radiotherapy (IGRT) workflows were assessed. The translational and rotational positioning errors for the different imaging workflows, 3D translational vectors and estimates of imaging dose delivered for the different imaging workflows were evaluated. Results: As the frequency of intra-fractional imaging increased from workflow 1 to 3, the mean intra-fraction 3D translational vector improved from 0.91 mm (±0.52 mm), to 0.64 (±0.34 mm). 85 %, 83 % and 97 % of images were within a tolerance of 1 mm/1° for workflows 1, 2 and 3 respectively, based on post treatment CBCT images. The average treatment time for workflow 3 was 13 min, as compared to 12 min for workflows 1 and 2. The effective dose per treatment for IGRT workflows 1, 2 and 3 measured 0.6 mSv, 0.95 mSv and 1.8 mSv respectively. Conclusion: The study demonstrated that the use of additional intra-fractional stereoscopic kilovoltage image-guidance during spinal SBRT, reduced the number of measurements deemed "out of tolerance" and treatment delivery could be optimized within a standard treatment timeslot without applying substantial additional radiation dose.