Plasma and milk metabolomics revealed changes in amino acid metabolism in Holstein dairy cows under heat stress.

Our understanding of metabolic alterations triggered by heat stress is incomplete, which limits the designing of nutritional strategies to mitigate negative productive and health effects. Thus, this study aimed to explore the metabolic responses of heat-stressed dairy cows to dietary supplementation with vitamin D3/Ca and vitamin E/Se. Twelve multiparous Holstein cows were enrolled in a split-plot Latin square design with two distinct vitamin E/Se supplementation levels, either at a low (ESe-, n = 6, 11.1 IU/kg vitamin E and 0.55 mg/kg Se) or a high dose (ESe+, n = 6 223 IU/kg vitamin E and 1.8 mg/kg Se) as the main plot. Treatment subplots, arranged in a replicated 3 × 3 Latin square design, comprised heat challenge (Temperature Humidity Index, THI: 72.0-82.0) supplemented with different levels of vitamin D3/Ca: either low (HS/DCa-, 1 012 IU/kg and 0.73%, respectively) or high (HS/DCa+, 3 764 IU/kg and 0.97%, respectively), and a pair-fed control group in thermoneutrality (THI = 61.0-64.0) receiving the low dose of vitamin D3/Ca (TN). The liquid chromatography-mass spectrometry-based metabolome profile was determined in blood plasma and milk sampled at the beginning (day 0) and end (day 14) of each experimental period. The results were analyzed for the effect of (1) TN vs. HS/ESe-/DCa-, and (2) the vitamin E/Se and vitamin D3/Ca supplementation. No group or group × day effects were detected in the plasma metabolome (false discovery rate, FDR > 0.05), except for triglyceride 52:2 being higher (FDR = 0.03) on day 0 than 14. Taurine, creatinine and butyryl-carnitine showed group × day interactions in the milk metabolome (FDR ≤ 0.05) as creatinine (+22%) and butyryl-carnitine (+190%) were increased (P < 0.01) on day 14, and taurine was decreased (-65%, P < 0.01) on day 14 in the heat stress (HS) cows, compared with day 0. Most compounds were unaffected by vitamin E/Se or vitamin D3/Ca supplementation level or their interaction (FDR > 0.05) in plasma and milk, except for milk alanine which was lower (-69%, FDR = 0.03) in the E/Se+ groups, compared with E/Se-. Our results indicated that HS triggered more prominent changes in the milk than in the plasma metabolome, with consistent results in milk suggesting increased muscle catabolism, as reflected by increased creatinine, alanine and citrulline levels. Supplementing with high levels of vitamin E/Se or vitamin D3/Ca or their combination did not appear to affect the metabolic remodeling triggered by HS.

Dietary supplementation of vitamin D3 and calcium partially recover the compromised time budget and circadian rhythm of lying behavior in lactating cows under heat stress.

Heat stress (HS) impedes cattle behavior and performance and is an animal comfort and welfare issue. The objective of this study was to characterize the time budget and circadian rhythm of lying behavior in dairy cows during HS and to assess the effect of dietary supplementation of vitamin D3 and Ca. Twelve multiparous Holstein cows (42.2 ± 5.6 kg milk/d; 83 ± 27 d in milk) housed in tiestalls were used in a split-plot design with the concentration of dietary vitamin E and Se as main plots (LESe: 11.1 IU/kg and 0.55 mg/kg, and HESe: 223 IU/kg and 1.8 mg/kg, respectively). Within each plot cows were randomly assigned to (1) HS with low concentrations of vitamin D3 and Ca (HS, 1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D3 and Ca (HS+D3/Ca; 3,764 IU/kg and 0.97%, respectively), or (3) thermoneutral pair-fed (TNPF) with low concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73%, respectively) in a Latin square design with 14-d periods and 7-d washouts. Lying behavior was measured with HOBO Loggers in 15-min intervals. Overall, cows in HS spent less time lying per day relative to TNPF from d 7 to 14. Daily lying time was positively correlated with milk yield, energy-corrected milk yield, and feed efficiency, and was negatively correlated with rectal temperature, respiratory rate, fecal calprotectin, tumor necrosis factor-α, and C-reactive protein. A treatment by time interaction was observed for lying behavior: the time spent lying was lesser for cows in HS than in TNPF in the early morning (0000-0600 h) and in the night (1800-2400 h). The circadian rhythm of lying behavior was characterized by fitting a cosine function of time into linear mixed model. Daily rhythmicity of lying was detected for cows in TNPF and HS+D3/Ca, whereas only a tendency in HS cows was observed. Cows in TNPF had the highest mesor (the average level of diurnal fluctuations; 34.2 min/h) and amplitude (the distance between the peak and mesor; 17.9 min/h). Both the mesor and amplitude were higher in HS+D3/Ca relative to HS (26.6 vs. 25.2 min/h and 3.91 min/h vs. 2.18 min/h, respectively). The acrophase (time of the peak) of lying time in TNPF, HS, and HS+D3/Ca were 0028, 0152, and 0054 h, respectively. Lastly, a continuous increase in daily lying time in TNPF was observed during the first 4 d of the experimental period in which DMI was gradually restricted, suggesting that intake restrictions may shift feeding behavior and introduce biases in the behavior of animals. In conclusion, lying behavior was compromised in dairy cows under HS, characterizing reduced daily lying time and disrupted circadian rhythms, and the compromised lying behavior can be partially restored by supplementation of vitamin D3 and Ca. Further research may be required for a more suitable model to study behavior of cows under HS.

[Should we switch from saline to lactated Ringer's solution? Limited benefits, medication warning system required]. / Moeten we over van NaCl 0,9% naar Ringer-lactaat?

In recent years, there has been a growing advocacy to implement the use of balanced solutions like lactated Ringer's solution instead of normal saline as fluid therapy in non-critically ill patients. Currently, evidence shows that there might be a limited benefit of the use of Lactated Ringer's solution over saline in both in critically ill and non-critically ill patients. Lactated Ringer's solution is, in contrast to saline, incompatible with blood products and various frequently used intravenously administered drugs. The use of these drugs in conjunction with lactated Ringer's solution therefore requires additional precautionary measures. A hospital-wide transition from saline to lactated Ringer's solution might be beneficial for a subset of patients. However, a medication warning system is required for safe implementation.

Increased dietary vitamin D3 and calcium partially alleviate heat stress symptoms and inflammation in lactating Holstein cows independent of dietary concentrations of vitamin E and selenium.

Twelve multiparous Holstein cows (42.2 ± 5.6 kg of milk/d; 83 ± 27 d in milk) were used in a split-plot design testing the effects of mineral and vitamin supplementation on the time course of animal performance, metabolism, and inflammation markers during heat stress. The main plot was the average concentrations of dietary vitamin E and Se (adequate: 11.1 IU/kg of vitamin E and 0.55 mg/kg of Se, and high: 223 IU/kg of vitamin E and 1.8 mg/kg of Se, respectively). Within each plot, cows were randomly assigned to (1) heat stress (HS) with adequate concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D3 and Ca (HS+D3/Ca; 3,764 IU/kg and 0.97%, respectively), or (3) pair-feeding (PF) in thermoneutrality with adequate concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73% Ca) in a Latin square design with 14-d periods and 7-d washouts. The highest rectal temperature was recorded at 1700 h for HS (39.4°C; mean of d 1 to 14), being 1.2 and 0.8°C greater than for PF and HS+D3/Ca, respectively. Respiratory rate and water intake were higher in HS (73 breaths/min and 115 L/d, respectively) relative to PF (28 breaths/min and 76 L/d). Heat stress decreased dry matter intake progressively, reaching a nadir on d 5 to 7 (33% reduction) and was not different between treatments. Milk yield decreased progressively in all treatments, but remained greater in PF relative to HS from d 3 to 14 (10%), whereas HS and HS+D3/Ca were not different. Milk fat, protein, and lactose concentrations and yields were lower in HS relative to PF from d 3 to 14, but not different between HS and HS+D3/Ca. Relative to PF, preprandial insulin concentrations were increased in HS, whereas plasma nonesterified fatty acids were decreased on d 7 and 14. Plasma lipopolysaccharide-binding protein concentrations increased in HS cows on d 7 and 14, respectively, relative to PF, whereas they were reduced in HS + D3/Ca on d 14. Plasma C-reactive protein, tumor necrosis factor-α, and fecal calprotectin were increased in HS relative to both PF and HS+D3/Ca on d 7 and 14. Rectal temperature was positively associated with plasma lipopolysaccharide-binding protein (r = 0.72), tumor necrosis factor-α (r = 0.74), C-reactive protein (r = 0.87), and with milk somatic cells (r = 0.75). Plasma 8-hydroxy-2-deoxyguanosine concentrations presented a 3-way interaction, where 8-hydroxy-2-deoxyguanosine was lower in HS than in PF on d 7 and 14, and lower in HS+D3/Ca relative to HS on d 14 in the adequate vitamin E and Se treatment, but no effects were observed in the high vitamin E and Se group. Plasma superoxide dismutase concentrations increased over time, and were higher in HS relative to PF on d 14, whereas HS+D3/Ca was similar to HS. Heat stress markedly reduced milk production and milk components while increasing markers of leaky gut and inflammation. In contrast, vitamin D3 and Ca supplementation reduced hyperthermia (d 7-14), markers of leaky gut, and inflammation independent of dietary concentrations of vitamin E and Se.

Effects of direct-fed Bacillus subtilis and Bacillus licheniformis on production performance and milk fatty acid profile in dairy cows.

The aim of the study was to determine the effect of a Bacillus-based direct-fed microbial on performance of mid-lactating Holstein dairy cows and on their milk fatty acid composition. Six multiparous cows fitted with a rumen cannula were used in a randomized replicated crossover design. Cows received 200 g/d of either whey powder as a control or BioPlus 2B (Chr. Hansen), a commercial direct-fed microbial providing Bacillus subtilis and Bacillus licheniformis, representing a daily dose of 6.4 × 1011 cfu, and using whey powder as a carrier. The 2 experimental periods lasted 14 d and were separated by a 7-d washout interval. Samples were collected on d 0, 13, and 14 of each period. Data from d 0 were used as covariate. Significance was declared at P ≤ 0.05 and tendency at 0.05

The impact of environmental and nutritional stresses on milk fat synthesis in dairy cows.

Stress reduces milk and milk components synthesis and increases maintenance requirements of cows. The major stress-related alterations involve enhanced secretion of glucocorticoids and increased sympathetic nervous system activity, which results in biochemical and physiologic changes. In dairy cows exposed to social (ie housing conditions, overstocking, regrouping, feed delivery), physiological (ie initiation of lactation and parturition), or physical (ie heat or cold stress) stressors, responses involve alterations in energy balance and nutrient partitioning. The capacity of the animal to synthesize milk fat largely depends on the availability of substrates for lipid synthesis from the diet, ruminal fermentation or adipose tissue stores, all of which can be altered under stress conditions. Indeed, milk fat concentration is particularly responsive to diet and environment modifications, where a wide range of nutritional and non-nutritional factors influence milk fat output. Milk fat synthesis is an energy demanding process, and extremely sensitive to stress factors during lactation and the involvement of multiple organs. Recent studies examining social, physical, and physiological stressors have provided important insights into how differences in milk yield and milk components may be associated with biological responses to stress factors in dairy cows. This review focuses primarily on the role of stress sources and indicators to which the dairy cow is exposed in regulating milk fat synthesis. We will review the role of nutritional and non-nutritional factors on milk fat synthesis in dairy cows under stress conditions.

Effect of dietary supplementation or cessation of magnesium-based alkalizers on milk fat output in dairy cows under milk fat depression conditions.

We aimed to evaluate the effects of dietary supplementation with magnesium oxide and calcium-magnesium dolomite on milk fat synthesis and milk fatty acid profile or persistency in milk fat synthesis after their cessation in dairy cows under milk fat depression conditions. Twenty-four multiparous dairy cows in early lactation (mean ± standard deviation; 112 ± 14 d in milk) were used in a randomized complete block design. Milk fat depression was induced in all cows for 10 d by feeding a diet containing 35.2% starch, 28.7% neutral detergent fiber, and 4.8% total fatty acid (dry matter). The experiment was conducted in 2 periods. During the Mg-supplementation period (d 1-20), cows were randomly assigned to (1) the milk fat depression diet used during the induction phase (control; n = 8), (2) the control diet plus 0.4% magnesium oxide (MG; n = 8), or (3) the control diet plus 0.8% calcium-magnesium dolomite (CMC; n = 8). Compared with the control group, feeding the magnesium-supplemented diets increased milk fat concentration and yield by 12% within 4 d. During the 20-d Mg-supplementation period, both the MG and CMC diets increased milk fat concentration and yield, as well as 3.5% fat-corrected milk and energy-corrected milk yield, without affecting dry matter intake, milk yield, and milk protein and lactose concentrations. In the Mg-cessation period (d 21-30), all cows received the control diet, which resulted in a greater milk fat concentration and yield in the cows that had already received the MG and CMC diets in the Mg-supplementation period. Whereas, milk fat concentration and yield remained high after discontinuation of the magnesium-containing alkalizer until d 27. The difference in milk fat synthesis was associated with lower trans-10 C18:1 (-22%) and higher trans-11 C18:1 (+12.5%) concentrations in milk during the Mg-supplementation period. Furthermore, it was evident that within 2 d of supplementation, the trans-10:trans-11 ratio was lower in MG and CMC cows compared with cows receiving the control. This suggested that the effect of magnesium-based alkalizers on milk fat synthesis was mediated via a shift in ruminal biohydrogenation of cis-9,cis-12 C18:2 in the rumen. In conclusion, abrupt addition of magnesium oxide and calcium-magnesium dolomite increased milk fat synthesis, which persisted for 7 d after cessation of magnesium-based alkalizers. A similar ability to recover milk fat synthesis and normal fatty acid biohydrogenation pathways was observed for magnesium oxide and calcium-magnesium dolomite.

Potassium carbonate as a supplement to improve milk fat concentration and yield in early-lactating dairy goats fed a high-starch, low-fiber diet.

This study investigated the use of K2CO3 as dietary buffer to prevent or to recover from low milk fat production when early-lactating dairy goats are fed a high-starch, low-fiber (HSLF) diet. At kidding, 30 Alpine goats housed in pens with Calan gate feeders received a total mixed ration with a forage-to-concentrate ratio of 55:45 on a dry matter (DM) basis for a baseline period of 27 ± 4 d. Goats (milk yield, 4.14 ± 0.88 kg/d; milk fat, 4.28 ± 0.52%; mean ± SD) were then assigned to 1 of 10 blocks according to parity (first vs. second or more) and milk fat concentration, and fed a HSLF diet containing 45% forages and 55% concentrates for 2 experimental periods of 28 d. Treatments were identified as (1) control, in which the HSLF diet was fed throughout both periods; (2) preventive, in which the HSLF diet supplemented with K2CO3 (1.6% of DM) was fed during both periods; and (3) recovery, in which the HSLF diet was fed during the first period (P1) and the HSLF diet supplemented with K2CO3 was fed during the second period (P2). Data from P1 and P2 were analyzed separately. In P1, preplanned contrasts were used to evaluate the preventive effect of K2CO3 (control and recovery, both groups receiving the same diet during this period, vs. preventive), and in P2, to assess the potential of K2CO3 to alleviate an already existing state of low milk fat (control vs. recovery and preventive vs. recovery). Feeding the HSLF diet in P1 moderately decreased milk fat concentration (-16%) and yield (-13%) as compared with baseline. Dietary addition of K2CO3 decreased DM intake by 12 and 14% in P1 and P2, respectively. Ruminal pH was not different among treatments. There was also no significant difference in milk yield (4.13 and 3.71 kg/d on average in P1 and P2, respectively) for any tested contrasts. In P1, milk fat concentration and yield did not differ among goats fed control (3.58% and 151 g/d, respectively) and preventive (3.67% and 148 g/d, respectively) diets. In P2, milk fat concentration and yield did not differ among goats fed the control diet (3.38% and 137 g/d, respectively), and diets where K2CO3 was used as preventive (3.44% and 126 g/d, respectively) or recovery treatment (3.25% and 113 g/d, respectively). Supplementing a high-concentrate diet with 1.6% K2CO3 was therefore not effective in either preventing or suppressing already existing conditions of low milk fat production in dairy goats.

Acerca del conocimiento sobre dolor en enfermeras de cuidados intensivos / About knowledge of intensive care unit nurses regarding pain

No disponible

[Parents' satisfaction in onco-hematology units]. / Satisfacción de los padres en unidades de oncohematología.

INTRODUCTION: patient satisfaction is a quality of care predictor that allows to identify specific areas of improvement. Frequently, parents are who provide this information when their children are too young or cannot communicate. The aim of the study was to determine parents' satisfaction with paediatric oncology care and its relationship with sociodemographic variables. MATERIAL AND METHODS: a cross-sectional observational study was carried out. Parents whose children suffered from cancer and were treated in the oncology ward and oncology day hospital in Asturias were included. A questionnaire with sociodemographic variables and the Cuestionario de Calidad de Cuidados de Enfermería (CUCACE), that evaluates experience and satisfaction with care through two dimensions (range from 0 to 100), were used. RESULTS: 24 parents agreed to particape. The average in experience dimension of CUCACE was 88,99 and 87,01 in satisfaction. All participants referred as positive the treat received at the units, however, 41,7% declared it should be enhanced. No relationship between satisfaction and sociodemographic variables were found. CONCLUSIONS: Parents of children with cancer demonstrated high satisfaction with care. Information and communication with medical staff need to be strengthened.

Analysis of Emergency Healthcare Demand in a Prison.

OBJECTIVE: To analyze the reasons for seeking emergency medical care amongst prison inmates and their relationship to sociodemographic characteristics. MATERIAL AND METHOD: An observational, descriptive and retrospective study was carried out. We collected the sociodemographic variables of inmates and their healthcare needs at the referral hospital over nine years. RESULTS: A total of 972 hospital visits were included. The most common healthcare needs, in descending order, were multiple trauma, limb problems and dyspnea. Mondays and Wednesdays were found to be the busiest days (P <0.001). The average stay in cases of hospitalization was 6.1 (SD: 4.3) days; patients with nontraumatic healthcare needs required a longer stay. The majority of the inmates native to Africa, Asia and America received emergency healthcare services due to traumatic injuries; by contrast the most common injuries among Europeans were non-traumatic and unrelated to suicide attempts (P <0.001). European inmates were on average 4.2 years older than Africans and 4.7 years older than American inmates (P <0.001). DISCUSSION: The reasons for seeking emergency care are clearly differentiated according to the inmates' nationality, one notable outcome was the greater longevity of European internees. These results highlight the importance of understanding healthcare demand within the prison system in order to better address considerations such as prevention, organization and the location of healthcare units.

Cyclin E expression is associated with high levels of replication stress in triple-negative breast cancer.

Replication stress entails the improper progression of DNA replication. In cancer cells, including breast cancer cells, an important cause of replication stress is oncogene activation. Importantly, tumors with high levels of replication stress may have different clinical behavior, and high levels of replication stress appear to be a vulnerability of cancer cells, which may be therapeutically targeted by novel molecularly targeted agents. Unfortunately, data on replication stress is largely based on experimental models. Further investigation of replication stress in clinical samples is required to optimally implement novel therapeutics. To uncover the relation between oncogene expression, replication stress, and clinical features of breast cancer subgroups, we immunohistochemically analyzed the expression of a panel of oncogenes (Cyclin E, c-Myc, and Cdc25A,) and markers of replication stress (phospho-Ser33-RPA32 and γ-H2AX) in breast tumor tissues prior to treatment (n = 384). Triple-negative breast cancers (TNBCs) exhibited the highest levels of phospho-Ser33-RPA32 (P < 0.001 for all tests) and γ-H2AX (P < 0.05 for all tests). Moreover, expression levels of Cyclin E (P < 0.001 for all tests) and c-Myc (P < 0.001 for all tests) were highest in TNBCs. Expression of Cyclin E positively correlated with phospho-RPA32 (Spearman correlation r = 0.37, P < 0.001) and γ-H2AX (Spearman correlation r = 0.63, P < 0.001). Combined, these data indicate that, among breast cancers, replication stress is predominantly observed in TNBCs, and is associated with expression levels of Cyclin E. These results indicate that Cyclin E overexpression may be used as a biomarker for patient selection in the clinical evaluation of drugs that target the DNA replication stress response.

Transient reductions in milk fat synthesis and their association with the ruminal and metabolic profile in dairy cows fed high-starch, low-fat diets.

Sub-acute ruminal acidosis (SARA) is sometimes observed along with reduced milk fat synthesis. Inconsistent responses may be explained by dietary fat levels. Twelve ruminally cannulated cows were used in a Latin square design investigating the timing of metabolic and milk fat changes during Induction and Recovery from SARA by altering starch levels in low-fat diets. Treatments were (1) SARA Induction, (2) Recovery and (3) Control. Sub-acute ruminal acidosis was induced by feeding a diet containing 29.4% starch, 24.0% NDF and 2.8% fatty acids (FAs), whereas the Recovery and Control diets contained 19.9% starch, 31.0% NDF and 2.6% FA. Relative to Control, DM intake (DMI) and milk yield were higher in SARA from days 14 to 21 and from days 10 to 21, respectively (P < 0.05). Milk fat content was reduced from days 3 to 14 in SARA (P < 0.05) compared with Control, while greater protein and lactose contents were observed from days 14 to 21 and 3 to 21, respectively (P < 0.05). Milk fat yield was reduced by SARA on day 3 (P < 0.05), whereas both protein and lactose yields were higher on days 14 and 21 (P < 0.05). The ruminal acetate-to-propionate ratio was lower, and the concentrations of propionate and lactate were higher in the SARA treatment compared with Control on day 21 (P < 0.05). Plasma insulin increased during SARA, whereas plasma non-esterified fatty acids and milk ß-hydroxybutyrate decreased (P < 0.05). Similarly to fat yield, the yield of milk preformed FA (>16C) was lower on day 3 (P < 0.05) and tended to be lower on day 7 in SARA cows (P < 0.10), whereas yield of de novo FA (<16C) was higher on day 21 (P < 0.01) in the SARA group relative to Control. The t10- to t11-18:1 ratio increased during the SARA Induction period (P < 0.05), but the concentration of t10-18:1 remained below 0.5% of milk fat, and t10,c12 conjugated linoleic acid remained below detection levels. Odd-chain FA increased, whereas branched-chain FA was reduced during SARA Induction from days 3 to 21 (P < 0.05). Sub-acute ruminal acidosis reduced milk fat synthesis transiently. Such reduction was not associated with ruminal biohydrogenation intermediates but rather with a transient reduction in supply of preformed FA. Subsequent rescue of milk fat synthesis may be associated with higher availability of substrates due to increased DMI during SARA.

Transcriptional effects of copy number alterations in a large set of human cancers.

Copy number alterations (CNAs) can promote tumor progression by altering gene expression levels. Due to transcriptional adaptive mechanisms, however, CNAs do not always translate proportionally into altered expression levels. By reanalyzing >34,000 gene expression profiles, we reveal the degree of transcriptional adaptation to CNAs in a genome-wide fashion, which strongly associate with distinct biological processes. We then develop a platform-independent method-transcriptional adaptation to CNA profiling (TACNA profiling)-that extracts the transcriptional effects of CNAs from gene expression profiles without requiring paired CNA profiles. By applying TACNA profiling to >28,000 patient-derived tumor samples we define the landscape of transcriptional effects of CNAs. The utility of this landscape is demonstrated by the identification of four genes that are predicted to be involved in tumor immune evasion when transcriptionally affected by CNAs. In conclusion, we provide a novel tool to gain insight into how CNAs drive tumor behavior via altered expression levels.

Abomasally infused SFA with varying chain length differently affect milk production and composition and alter hepatic and mammary gene expression in lactating cows.

The aim of the present study was to compare the effects of post-ruminally infused fat supplements, varying in fatty acid (FA) chain length, on animal performance, metabolism and milk FA. Eleven multiparous Holstein dairy cows were used in a replicated incomplete 3 × 3 Latin square design with 7-d periods, separated by 7-d washouts. Treatments were administered as abomasal infusions of enrichments providing 280 g/d of FA: (1) palmitic acid (98·4 % 16 : 0; PA), (2) caprylic and capric acids (56·2 % 8 : 0, 43·8 % 10 : 0; medium-chain TAG (MCT)) and (3) stearic acid (99·0 % 18 : 0; SA). Relative to PA, SA decreased the efficiency of fat-corrected milk production, which was associated with a tendency for higher DM intake and lower FA absorption with SA, whereas MCT was not different from PA for these variables. Milk fat concentration and yield were increased by PA relative to SA, but only fat yield tended to be greater relative to MCT. Relative to PA, MCT increased milk fat concentration of FA < 16 C, whereas SA increased FA > 16 C. Expression of mammary stearoyl-coA desaturase 1 was lower with SA than with PA. Relative to PA, liver expression of adenosine monophosphate-activated protein kinase-1 and pyruvate kinase was increased with MCT, whereas expression of these genes tended to be increased by SA. The mechanism of increased fat secretion with PA does not seem to be related to a modulation of the expression of lipogenesis-related genes, but rather to increased substrate availability as reflected by milk FA profile.

Consideration of breast cancer subtype in targeting the androgen receptor.

The androgen receptor (AR) is a drug target in breast cancer, and AR-targeted therapies have induced tumor responses in breast cancer patients. In this review, we summarized the role of AR in breast cancer based on preclinical and clinical data. Response to AR-targeted therapies in unselected breast cancer populations is relatively low. Preclinical and clinical data show that AR antagonists might have a role in estrogen receptor (ER)-negative/AR-positive tumors. The prognostic value of AR for patients remains uncertain due to the use of various antibodies and cut-off values for immunohistochemical assessment. To get more insight into the role of AR in breast cancer, we additionally performed a retrospective pooled analysis to determine the prognostic value of the AR using mRNA profiles of 7270 primary breast tumors. Our analysis shows that a higher AR mRNA level is associated with improved disease outcome in patients with ER-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, but with worse disease outcome in HER2-positive subgroups. In conclusion, next to AR expression, incorporation of additional tumor characteristics will potentially make AR targeting a more valuable therapeutic strategy in breast cancer.

In vitro approach for evaluation of carob by-products as source bioactive ingredients with potential to attenuate metabolic syndrome (MetS).

The potential bioactivities for alleviating Metabolic Syndrome associated risk factors were evaluated in carob (Ceratonia siliqua L.) fruit by-products, i.e. seed peel, germ and pod. Carob germ and seed peel showed higher phenolic content than pod (99.72, 80.24 and 47.06 µmol GAE g-1, respectively). Pod mostly contained gallic acid and gallotannins; seed peel and germ's showed as most abundant polyphenols quercetin and apigenin derivatives. Carob pod and seed peel revealed stronger antioxidant capacities compared to germ. The strongest antihypertensive activity was found in seed peel, followed by pod and germ. Anti-inflammatory activity showed inhibition of NO production in LPS-induced macrophages, although only pod was able of reducing pro-inflammatory mediators (TNF-α andPGD2). Finally, fat accumulation on mature adipocytes was reduced by carob seed peel and pod extracts. This work shows the potential use of pod carob by-products as food ingredients with special relevance of carob pod for attenuating metabolic syndrome.

Considering the biology of late recurrences in selecting patients for extended endocrine therapy in breast cancer.

Extended endocrine therapy can reduce recurrences occurring more than 5 years after diagnosis (late recurrences) in estrogen receptor (ER)-positive breast cancer. Given the side effects of endocrine therapy, optimal patient selection for extended treatment is crucial. Enhanced understanding of late recurrence biology could optimize patient selection in this setting. We therefore summarized the current knowledge of late recurrence biology, clinical trials on extended endocrine therapy, and tools for predicting late recurrence and benefit from treatment extension. Extending 5 years of tamoxifen therapy with 5 years of tamoxifen or an aromatase inhibitor (AI) reduces late recurrence risk by 2-5%, but results of extending AI-based therapy are inconsistent. Although several clinicopathological parameters and multigene assays are prognostic for late recurrence, selection tools predicting benefit from extended endocrine therapy are sparse. Therefore, we additionally performed a pooled analysis using 2231 mRNA profiles of patients with ER-positive/human epidermal growth factor receptor 2-negative breast cancer. Gene Set Enrichment Analysis was applied on genes ranked according to their association with early and late recurrence risk. Higher expression of estrogen-responsive genes was associated with a high recurrence risk beyond 5 years after diagnosis when patients had received no systemic therapy. Although 5 years of endocrine therapy reduced this risk, this effect disappeared after treatment cessation. This suggests that late recurrences of tumors with high expression of estrogen-responsive genes are likely ER-driven. Long-term intervention in this pathway by means of extended endocrine therapy might reduce late recurrences in patients with tumors showing high expression of estrogen-responsive genes.

Effect of magnetic ion exchange (MIEX®) on removal of emerging organic contaminants.

In this study, the removal of nine emerging organic contaminants was investigated by using anion exchange resins. The selected compounds were carbamazepine, atrazine, simazine, estrone, bisphenol A, methylparaben, ethylparaben, propylparaben and butylparaben. Two different magnetic anionic exchanger resins were tested: MIEX® DOC and MIEX® GOLD. The optimal resin dose (40 mL/L) and contact time (20 min) had been previously determined. Once these optimum parameters were set, the effect of the initial concentration of contaminants on the removal efficiency of the contaminants by the resins was studied. The study was carried out using mono and multicomponent systems, with distilled water and natural waters, to which contaminants had been previously added, in order to evaluate the competitive and matrix effects. Results showed that the average removal percentages obtained with the MIEX® DOC resin were: 51%, 61%, 68% and 80% for methyl-, ethyl-, propyl-, and butylparaben, respectively. For bisphenol A the result was similar, i.e., 66%, whereas for the rest of the compounds studied, removal efficiencies lower than 15% were obtained. The MIEX® GOLD resin achieved lower elimination rates than the MIEX® DOC resin in all cases.