Feeding rumen-protected methionine during the peripartum period improved milk fat content and reduced the culling rate of Holstein cows in a commercial herd.

Researchers have reported the benefits of feeding rumen-protected methionine (RPM) during the peripartum on the health parameters of dairy cows. Rumen-protected methionine has reportedly improved milk yield, milk components and liver health, but the literature is scarce on its effects in commercial herds. Therefore, we aimed to determine the effects of feeding RPMet (Smartamine M®, Adisseo Inc., Antony, France) prepartum (8 g per cow per day) and postpartum (15 g per cow per day) on performance, metabolic profile, and culling rate of Holstein cows in a commercial herd. One-hundred and 66 (n = 166) Holstein cows, 58 nulliparous and 108 parous, were randomly assigned to 1 of 2 dietary treatments, consisting of TMR top-dressed with RPMet (2.35 and 2.24% Met of MP for close-up and fresh cows, respectively) or without (control, CON, (2.03 and 1.89% Met of MP for close-up and fresh cows, respectively), fed from 21 ± 6 d prepartum until 16 ± 5 d postpartum. From 17 d in milk (DIM) until dry-off, all cows received RPMet. Daily milk yield was recorded, and milk samples were collected in the first and second weeks after calving to determine their composition. Blood samples were collected before the morning feeding on -14, -7, +1, +7, and +14 d relative to calving. Mortality and morbidity were recorded during the first 60 DIM. Cows supplemented with RPMet had greater milk yield during the first 16 DIM (31.76 vs. 30.37 kg/d; SEM = 1.04, respectively), and had greater milk fat content (4.45 vs. 4.10%; SEM = 0.11, respectively), but not milk total protein (3.47 vs. 3.39%; SEM = 0.04, respectively) and casein contents (2.74 vs. 2.66%; SEM = 0.04, respectively) than CON cows. Cows in RPMet had increased plasma Met concentrations than cows in CON (24.9 vs. 21.0 µmol/L; SEM = 1.2, respectively). Although morbidity was similar between treatments, the culling rate from calving until 60 DIM was lower for RPMet cows than for CON cows (2.4 vs. 12.1%; SEM = 0.02). In conclusion, cows receiving RPMet have greater milk yield, improved milk fat content, and a lower culling rate at 60 DIM than CON cows.

Seizing the moment: The time for harnessing electronic patient-reported outcome measures for enhanced and sustainable metastatic breast cancer care is now.

The sustainability of healthcare systems is under pressure. Unlike care for many other chronic diseases, cancer care has yet to empower patients in effectively self-managing both the medical and emotional consequences of their condition, including adapting to changes in lifestyle and work, which is essential to achieve optimal health and recovery. Although proposed as a potential solution for sustainable healthcare and support for optimal health and recovery already decades ago, practical implementation of digital care lags behind. We believe electronic patient reported outcome measures (ePROMs) could play an important role in creating sustainable healthcare, both to guide complex treatment pathways and to empower survivors to self-manage consequences of diagnosis and treatment. That is, ePROMs can be used for screening and monitoring of symptoms, but also for treatment decision-making and to facilitate communication about quality of life. We therefore see opportunities for improvements in quality of care, quality of life, and survival of cancer patients, as well as research opportunities, as ePROMs collection can lead to better understanding of care needs. The '10 Actions for Change report' of the Advanced Breast Cancer Global Alliance stresses a critical need for improvement of care for metastatic breast cancer (MBC) patients. We therefore in this paper focus on MBC care and research.

Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522.

BACKGROUND: KEYNOTE-522 demonstrated statistically significant improvements in pathological complete response (pCR) with neoadjuvant pembrolizumab plus chemotherapy and event-free survival (EFS) with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with high-risk, early-stage triple-negative breast cancer (TNBC). Prior studies have shown the prognostic value of the residual cancer burden (RCB) index to quantify the extent of residual disease after neoadjuvant chemotherapy. In this preplanned exploratory analysis, we assessed RCB distribution and EFS within RCB categories by treatment group. PATIENTS AND METHODS: A total of 1174 patients with stage T1c/N1-2 or T2-4/N0-2 TNBC were randomized 2 : 1 to pembrolizumab 200 mg or placebo every 3 weeks given with four cycles of paclitaxel + carboplatin, followed by four cycles of doxorubicin or epirubicin + cyclophosphamide. After surgery, patients received pembrolizumab or placebo for nine cycles or until recurrence or unacceptable toxicity. Primary endpoints are pCR and EFS. RCB is a prespecified exploratory endpoint. The association between EFS and RCB was assessed using a Cox regression model. RESULTS: Pembrolizumab shifted patients into lower RCB categories across the entire spectrum compared with placebo. There were more patients in the pembrolizumab group with RCB-0 (pCR), and fewer patients in the pembrolizumab group with RCB-1, RCB-2, and RCB-3. The corresponding hazard ratios (95% confidence intervals) for EFS were 0.70 (0.38-1.31), 0.92 (0.39-2.20), 0.52 (0.32-0.82), and 1.24 (0.69-2.23). The most common first EFS events were distant recurrences, with fewer in the pembrolizumab group across all RCB categories. Among patients with RCB-0/1, more than half [21/38 (55.3%)] of all events were central nervous system recurrences, with 13/22 (59.1%) in the pembrolizumab group and 8/16 (50.0%) in the placebo group. CONCLUSIONS: Addition of pembrolizumab to chemotherapy resulted in fewer EFS events in the RCB-0, RCB-1, and RCB-2 categories, with the greatest benefit in RCB-2. These findings demonstrate that pembrolizumab not only increased pCR rates, but also improved EFS among most patients who do not have a pCR.

Comparative analysis of the use of natural and synthetic antioxidants in chicken meat: an update review.

The search for healthy foods has attracted the industry's attention to developing products that use natural ingredients, including natural antioxidants. Antioxidants act as free radicals or oxygen scavengers, inhibiting lipid oxidation and adversely affecting meat products' sensory and nutritional quality. Several synthetic antioxidants have been used in the meat industry; however, studies point to health risks related to their consumption. Such fact drives research into natural antioxidants extracted from grains, oilseeds, spices, fruits, and vegetables, which may have a health-promoting effect. This manuscript evaluates the effectiveness of several natural antioxidants in improving the quality and shelf life of chicken meat products during processing, storage, and distribution. The potential effects of natural antioxidants widely used in chicken products are also discussed. It can be concluded that these natural antioxidants are possible substitutes for synthetic ones. However, their use can affect the product's characteristics.

Feeding rumen-protected lysine prepartum alters placental metabolism at a transcriptional level.

Rumen-protected Lys (RPL) fed to Holstein cows prepartum resulted in a greater intake and improved health of their calves during the first 6 wk of life. However, whether increased supply of Lys in late gestation can influence placental tissue and, if so, which pathways are affected remain to be investigated. Therefore, we hypothesize that feeding RPL during late gestation could modulate placental metabolism, allowing for improved passage of nutrients to the fetus and thus influencing the offspring development. Therefore, we aimed to determine the effects of feeding RPL (AjiPro-L Generation 3, Ajinomoto Health and Nutrition North America) prepartum (0.54% DM of TMR) on mRNA gene expression profiles of placental samples of Holstein cows. Seventy multiparous Holstein cows were randomly assigned to 1 of 2 dietary treatments, consisting of TMR top-dressed with RPL (PRE-L) or without (control, CON), fed from 27 ± 5 d prepartum until calving. After natural delivery (6.87 ± 3.32 h), placentas were rinsed with physiological saline (0.9% sodium chloride solution) to clean any dirtiness from the environment and weighed. Then, 3 placentomes were collected, one from each placental region (cranial, central, and caudal), combined and flash-frozen in liquid nitrogen to evaluate the expression of transcripts and proteins related to protein metabolism and inflammation. Placental weights did not differ from cows in PRE-L (15.5 ± 4.03 kg) and cows in CON (14.5 ± 4.03 kg). Feeding RPL prepartum downregulated the expression of NOS3 (nitric oxide synthase 3), involved in vasodilation processes, and SOD1, which encodes the enzyme superoxide dismutase, involved in oxidative stress processes. Additionally, feeding RPL prepartum upregulated the expression of transcripts involved in energy metabolism (SLC2A3, glucose transporter 3; and PCK1, phosphoenolpyruvate carboxykinase 1), placental metabolism and cell proliferation (FGF2, fibroblast growth factor 2; FGF2R, fibroblast growth factor 2 receptor; and PGF, placental growth factor), Met metabolism (MAT2A, methionine adenosyltransferase 2-α), and tended to upregulate IGF2R (insulin-like growth factor 2 receptor). Placental FGF2 and LRP1 (low-density lipoprotein receptor-related protein 1) protein abundance were greater for cows that received RPL prepartum than cows in CON. In conclusion, feeding RPL to prepartum dairy cows altered uteroplacental expression of genes and proteins involved in cell proliferation, and in metabolism and transport of glucose. Such changes are illustrated by increased expression of SLC2A3 and PCK1 and increased protein abundance of FGF2 and LRP1 in uteroplacental tissue of cows consuming RPL.

Association of dry matter intake, milk yield, and days to first ovulation with cytological endometritis in Holstein cows.

Dry matter intake (DMI, kg/d) is closely related to the magnitude of negative energy and protein balance during the transition period, and the metabolic adaptations to support lactation in dairy cows. Thus, DMI might affect the development of cytological endometritis in the early postpartum period. Difficulty to adapt to these metabolic changes is related to impaired immune function and increased occurrence of reproductive disorders. We aimed to examine the association of pre- and postpartum DMI, body weight (BW), body condition score, milk yield and milk composition, and days to first ovulation with cytological endometritis at 15 (CYT15) and 30 DIM (CYT30). A second objective was to understand the association of vaginal discharge with CYT15 and CYT30 and performance. We conducted a pooled statistical analysis of 5 studies, including data from 280 multiparous Holstein cows. Based on the cutoffs for the percentage of uterine polymorphonuclear cells (PMN), determined by taking the median value of the data set for 15 and 30 DIM, cows were categorized as follows: LOW15 (PMN % at 15 DIM ≤24%; n = 125), HIGH15 (PMN % at 15 DIM >24%; n = 125), LOW30 (PMN % at 30DIM ≤7%; n = 141); and HIGH30 (PMN % at 30DIM >7%; n = 139). Cows in HIGH15 consumed an average of 1.97 ± 0.5 kg/d less DM than cows in LOW15 during prepartum, and 3.01 ± 0.5 kg/d less DM during postpartum. Dry matter intake (as a percentage of BW) was higher for cows in LOW15 during pre- and postpartum than for cows in HIGH15. Moreover, cows in HIGH15 tended to have lower milk yield than cows in LOW15 from the third until the fifth week postpartum. Although DMI was not associated with CYT30, DMI (as a percentage of BW) was lower for cows in LOW30 pre- and postpartum than for cows in HIGH30. There was no association between CYT30 and milk yield. Cows in LOW15 had greater days to first ovulation than cows in HIGH15, while cows in LOW30 also had greater days to first ovulation than cows in HIGH30. Simple regression analyses demonstrated linear associations of increased DMI, particularly postpartum, with decreased uterine PMN percentage and lower vaginal discharge score. Additionally, increased units of vaginal discharge score and increased percentage units of uterine PMN were linearly associated with decreased milk yield. Corroborating with the notion of the ovarian function being associated with uterine inflammatory status, cows in HIGH15 and HIGH30 ovulated on average 3 d before than cows in LOW15 and LOW30, respectively. Cytological endometritis at 15 DIM was associated with lower DMI from 4 wk before calving until 4 wk postpartum and was associated with lower milk yield. The association of vaginal discharge with cytological endometritis was variable and dependent on the day of evaluation.

Changes over time in self-efficacy to cope with cancer and well-being in women with breast cancer: a cross-cultural study.

OBJECTIVE: This study aimed to examine whether self-efficacy to cope with cancer changes over time in patients with breast cancer and whether these potential changes are similar across patients. It also aimed to examine whether these trajectories are related to patient psychological well-being and overall quality of life. METHODS: Participants (N = 404) from four countries (i.e. Finland, Israel, Italy, and Portugal) were enrolled in the study few weeks after breast surgery or biopsy. Self-efficacy to cope with cancer was assessed at baseline, six and 12 months later. Well-being indices were assessed at baseline, 12 and 18 months later. RESULTS: Using Latent Class Growth Analysis, two groups of patients were identified. The majority of patients reported high levels of self-efficacy to cope, which increased over time. For almost 15% of the patients, however, self-efficacy declined over time. Diminishing levels of self-efficacy to cope predicted worse levels of well-being. The pattern of self-efficacy changes and their relationships to well-being was consistent across countries. CONCLUSION: Monitoring self-efficacy to cope with cancer is probably important in order to detect alarming changes in its levels, as a declining self-efficacy to cope may serve as a signal of the need for intervention to prevent adaptation difficulties.

Holistic profiling of the venom from the Brazilian wandering spider Phoneutria nigriventer by combining high-throughput ion channel screens with venomics.

Introduction: Spider venoms are a unique source of bioactive peptides, many of which display remarkable biological stability and neuroactivity. Phoneutria nigriventer, often referred to as the Brazilian wandering spider, banana spider or "armed" spider, is endemic to South America and amongst the most dangerous venomous spiders in the world. There are 4,000 envenomation accidents with P. nigriventer each year in Brazil, which can lead to symptoms including priapism, hypertension, blurred vision, sweating, and vomiting. In addition to its clinical relevance, P. nigriventer venom contains peptides that provide therapeutic effects in a range of disease models. Methods: In this study, we explored the neuroactivity and molecular diversity of P. nigriventer venom using fractionation-guided high-throughput cellular assays coupled to proteomics and multi-pharmacology activity to broaden the knowledge about this venom and its therapeutic potential and provide a proof-of-concept for an investigative pipeline to study spider-venom derived neuroactive peptides. We coupled proteomics with ion channel assays using a neuroblastoma cell line to identify venom compounds that modulate the activity of voltage-gated sodium and calcium channels, as well as the nicotinic acetylcholine receptor. Results: Our data revealed that P. nigriventer venom is highly complex compared to other neurotoxin-rich venoms and contains potent modulators of voltage-gated ion channels which were classified into four families of neuroactive peptides based on their activity and structures. In addition to the reported P. nigriventer neuroactive peptides, we identified at least 27 novel cysteine-rich venom peptides for which their activity and molecular target remains to be determined. Discussion: Our findings provide a platform for studying the bioactivity of known and novel neuroactive components in the venom of P. nigriventer and other spiders and suggest that our discovery pipeline can be used to identify ion channel-targeting venom peptides with potential as pharmacological tools and to drug leads.

Feeding rumen-protected lysine altered immune and metabolic biomarkers in dairy cows during the transition period.

This experiment was conducted to determine the effects of feeding rumen-protected lysine (RPL; AjiPro-L Generation 3, Ajinomoto Health and Nutrition North America Inc.) from -26 ± 4.6 d prepartum (0.54% RPL of dietary dry matter intake) to 28 d postpartum (0.39% RPL of dietary dry matter intake) on immunometabolic status and liver composition in dairy cows. Seventy-five multiparous Holstein cows, blocked by parity, previous 305-d mature-equivalent milk production, expected calving date, and body condition score during the far-off dry period were assigned to 1 of 4 dietary treatments in a randomized, complete block design with a 2 × 2 factorial arrangement of treatments. Treatments prepartum consisted of total mixed ration top dressed with RPL (PRE-L) or without RPL (PRE-C), and postpartum treatments consisted of total mixed ration top dressed PRE-L prepartum and postpartum, PRE-L prepartum and PRE-C postpartum, PRE-C prepartum and PRE-L postpartum, and PRE-C prepartum and postpartum in 300 g of molasses. Blood samples were taken on -7 ± 0.5, 0 ± 0.5, 7 ± 0.9, 14 ± 0.9, and 28 ± 0.5 d relative to calving. Whole blood samples were taken on -14 ± 0.5, -7 ± 0.5, 7 ± 0.9, and 14 ± 0.9 d relative to calving for oxidative burst and phagocytic capacity of monocytes and neutrophils. Liver samples were collected via a biopsy on -12 ± 4.95 and 13 ± 2.62 d relative to calving and analyzed for liver composition (triacylglyceride and carnitine concentrations), mRNA expression of hepatic genes, and protein abundance. Protein abundance was calculated by normalizing intensity bands for a specific protein with glyceraldehyde-3-phosphate dehydrogenase. Concentrations of haptoglobin and glutathione peroxidase activity in plasma were lower at d 0 for cows in PRE-L (102 µg/mL and 339 nmol/min per mL, respectively) compared with cows in PRE-C (165 µg/mL and 405 nmol/min per mL, respectively). Oxidative burst capacity in monocytes tended to be greater on d 7 postpartum for cows in PRE-L (65.6%) than cows in PRE-C (57.5%). Additionally, feeding RPL altered the mRNA expression in liver tissue prepartum [decreased INSR (insulin receptor), CPT1A (carnitine palmitoyltransferase 1A), and IL1B (interleukin 1 ß)] and postpartum [increased IL8 (interleukin 8), EHMT2 (euchromatic histone lysine methyltransferase 2), TSPO (translocator protein), and SLC3A2 (solute carrier family 3 member 2); and decreased SLC7A1 (solute carrier family 7 member 1), SOD1 (superoxide dismutase 1), and SAA3 (serum amyloid A 3)] compared with cows not consuming RPL]. Additionally, cows in the PRE-C prepartum and PRE-L postpartum treatment tended to have greater protein abundance of mTOR postpartum compared with the PRE-C prepartum and postpartum treatment. Protein abundance of SLC7A7 (solute carrier family 7 member 7) pre- and postpartum tended to be greater and BBOX1 (gamma-butyrobetaine dioxygenase 1) tended to be less when RPL was consumed prepartum. In conclusion, cows that consumed RPL during the transition period had molecular changes related to liver composition, enhanced liver function indicated by greater total protein and albumin concentrations in plasma, and improved immune status indicated by decreased haptoglobin, glutathione peroxidase activity, and immune related mRNA expression.

International development of a patient-centered core outcome set for assessing health-related quality of life in metastatic breast cancer patients.

PURPOSE: For patients living with metastatic breast cancer (MBC), achieving best possible health-related quality of life, along with maximizing survival, is vital. Yet, we have no systemic way to determine if we achieve these goals. A Core Outcome Set (COS) that allows standardized measurement of outcomes important to patients, but also promotes discussing these outcomes during clinical encounters, is long overdue. METHODS: An international expert group (EG) of patient advocates, researchers, medical specialists, nurse specialists, and pharmaceutical industry representatives (n = 17) reviewed a list of relevant outcomes retrieved from the literature. A broader group (n = 141: patients/patient advocates (n = 45), health care professionals/researchers (n = 64), pharmaceutical industry representatives (n = 28), and health authority representatives (n = 4)) participated in a modified Delphi procedure, scoring the relevance of outcomes in two survey rounds. The EG finalized the COS in a consensus meeting. RESULTS: The final MBC COS includes 101 variables about: (1) health-related quality of life (HRQoL, n = 26) and adverse events (n = 24); (2) baseline patient characteristics (n = 9); and (3) clinical variables (n = 42). Many outcome that cover aspects of HRQoL relevant to MBC patients are included, e.g. daily functioning (including ability to work), psychosocial/emotional functioning, sexual functioning, and relationship with the medical team. CONCLUSION: The COS developed in this study contains important administrative data, clinical records, and clinician-reported measures that captures the impact of cancer. The COS is important for standardization of clinical research and implementation in daily practice and has received accreditation by the International Consortium for Health Outcomes Measurement (ICHOM).

The mutual determination of self-efficacy to cope with cancer and cancer-related coping over time: a prospective study in women with breast cancer.

OBJECTIVE: The aim of this study was to examine the longitudinal impact of self-efficacy to cope with cancer on the cancer-related coping reactions of breast cancer patients and vice versa. DESIGN AND MAIN OUTCOMES MEASURES: Data from the BOUNCE Project (https://www.bounce-project.eu/) were used to address the hypotheses. Participants (N = 403) were enrolled in the study a few weeks after surgery or biopsy. Coping self-efficacy was assessed at baseline and six months later (M6). Cancer-related coping was assessed three (M3) and nine months (M9) after baseline. The analyses were performed using structural equation modeling with Mplus 8.6. RESULTS: Baseline coping self-efficacy predicted all M3 coping reactions, while M6 coping self-efficacy also predicted changes in all but one M9 coping reaction. Moreover, one of the M3 coping reactions, that is, hopelessness/helplessness, predicted the changes in M6 coping self-efficacy. The relation between coping self-efficacy and one coping reaction (i.e. cognitive avoidance) was rather weak. Stability paths from M3 to M9 coping reactions were moderate to high. CONCLUSION: The relationship between self-efficacy to cope with cancer and cancer-related coping is complex. New theoretical models are needed to more accurately describe the diverse aspects of this association.

The Interplay Between Trait Resilience and Coping Self-efficacy in Patients with Breast Cancer: An International Study.

The role of self-efficacy to cope with breast cancer as a mediator and/or moderator in the relationship of trait resilience to quality of life and psychological symptoms was examined in this study. Data from the BOUNCE Project ( https://www.bounce-project.eu/ ) were used. Women diagnosed with and in treatment for breast cancer (N = 484), from four countries, participated in the study. Trait resilience and coping self-efficacy were assessed at baseline (soon after the beginning of systemic treatment), and outcomes (quality of life, psychological symptoms) 3 months later. Hierarchical regression, mediation, moderation, and conditional (moderated) mediation and moderation analyses were performed to examine the study hypotheses. Coping self-efficacy mediated the impact of trait resilience. In addition, higher levels of resilience in combination with higher levels of coping self-efficacy were associated with better outcomes. Country of origin had no impact on these results. Overall, it seems that coping self-efficacy is a key factor that should be taken into account for research and intervention efforts in cancer.

Effects of dietary energy density and feeding strategy during the dry period on feed intake, energy balance, milk production, and blood metabolites of Holstein cows.

Our study aimed to assess the effects of dietary energy density and strategy of delivery during the dry period on production and metabolic responses of Holstein cows free of displacement of abomasum, retained placenta, metritis, or hypocalcemia. Twenty-seven multiparous cows dried-off 50 d before calving were assigned randomly to 1 of 3 dietary treatments: a controlled energy, high-fiber diet [CE; 1.39 Mcal net energy for lactation (NEL)/kg of dry matter (DM)] formulated to supply 100% of the NEL requirement at ad libitum intake; or a higher energy diet (1.58 Mcal/kg) fed either at ad libitum (HE) or restricted (RE) intake to supply ∼150 or 80% of the NEL requirements, respectively. After calving, all cows were fed the same lactation diet. Cows were individually fed and remained in the study until 28 d postpartum. Data were analyzed using 2 contrasts: CE versus HE (effect of diet composition in cows fed for ad libitum DM intake) and HE versus RE (effect of ad libitum or restricted intake of the same diet). Prepartum intakes of DM and NEL as well as energy balance (EB), were greater for HE than CE and greater for HE than RE. Body weight (BW) gain was higher in HE than in RE, but CE and HE did not differ. Change in body condition score did not differ between CE and HE or HE and RE. Postpartum intakes of DM and NEL, EB, BW, body condition score, calf birth BW, milk yield, and milk components did not differ between CE and HE or HE and RE. Concentrations of glucose, insulin, nonesterified fatty acids, ß-hydroxybutyrate, Ca, and Mg pre- and postpartum did not differ among diets. Although sample size was low, dry period plane of energy intake affected prepartum DM intake, EB, and BW gain but did not affect postpartum intakes of DM and NEL, yields of milk and milk components, or blood metabolites in healthy cows.

Validation of 2 urine pH measuring techniques in a prepartum negative dietary cation-anion difference diet and the relationship with production performance.

Negative dietary cation-anion difference (DCAD) diets have been implemented to combat hypocalcemia, a common peripartal disease in dairy cows; however, the extent of compensatory metabolic acidosis necessary and the subsequent effects on performance are still debated. Additionally, there is a need for an inexpensive, accurate method to measure urine pH on farm during the prepartum period to assess the extent of metabolic acidosis achieved by negative DCAD diets. Therefore, this experiment was conducted to determine the accuracy of Fisher pH sticks (pHF; ThermoFisher Scientific) and pHion balance test strips (pHI; pHion Balance) compared with a portable pH meter (pHP; Accumet AP115, ThermoFisher Scientific) in measuring urine pH (UpH) and the effect of UpH on pre- and postpartum dry matter intake (DMI), milk, and milk composition yields. Cows consumed a total mixed ration with a DCAD of -118 mEq/kg for 4 wk prepartum and 397 mEq/kg for 4 wk postpartum. Prepartum UpH measurements (n = 75) for each cow were averaged and used to classify cows in terms of urine pH as low (UpH ≤5.54; mean ± standard deviation; 5.44 ± 0.07), medium (UpH >5.54 and ≤5.90; 5.67 ± 0.09), or high (UpH >5.90; 6.42 ± 0.36). Cows were milked twice a day, and milk samples were taken on d 7 ± 1.3, 14 ± 1.4, and 28 ± 1.1 relative to calving. Milk yield and DMI were recorded daily and averaged weekly. Bland-Altman plots and Lin's concordance correlation coefficient (CCC) were used to assess the agreement between pHP and pHF or pHI (n = 375). Receiver operating characteristic curves were used to determine the threshold with pHF and pHI that best discriminated between UpH >5.75 and ≤5.75 compared with pHP, and area under the curve (AUC) was used to assess the accuracy. At the UpH threshold of 5.75 for pHF and pHI, the sensitivity, specificity, and AUC were 89.5 and 87.4, 99.1 and 97.0, and 0.94 and 0.92, respectively. The CCC was 0.93 for pHF and pHI, indicating near-perfect agreement with pHP. The UpH did not affect pre- or postpartum DMI. There was a tendency for a UpH × week interaction for milk yield, in which milk yields were less for cows in the low and medium groups. In conclusion, pHI and pHF are accurate measurements for UpH, and UpH did not affect DMI; however, when UpH was low or medium, milk yield was decreased at wk 1 postpartum.

Effect of feeding rumen-protected lysine through the transition period on postpartum uterine health of dairy cows.

Feeding rumen-protected methionine as an indispensable amino acid source has been shown to improve reproductive performance in dairy cows, but the effect of feeding rumen-protected lysine (RPL) during the peripartum period on reproductive performance is not well explored. Therefore, we aimed to determine the effects of feeding RPL (AjiPro-L Generation 3, Ajinomoto Heartland Inc.) prepartum, postpartum, or both on follicular dynamics, uterine health, and mRNA gene expression of the endometrium. Seventy-five multiparous Holstein cows were assigned to 1 of 2 dietary treatments with or without RPL in a randomized, complete block design. A 2 × 2 factorial arrangement of treatments was used. Prepartum (-28 d to calving), animals were fed a diet (68% of dietary DM from forage) with RPL [PRE-L; 0.54% RPL of dietary dry matter intake] or without RPL (PRE-C). After calving, half of the cows from each prepartum treatment group were assigned to a diet (56% forage) with RPL (PRE-L POST-L; PRE-C POST-L; 0.40% RPL of dietary dry matter intake) or without RPL (PRE-C POST-C; PRE-L POST-C) until 28 d in milk (DIM). Vaginal discharge was detected with a Metricheck device (Simcro) to detect metritis, and at 28 DIM polymorphonuclear leukocytes were evaluated as a percentage of the epithelial cells using a cytology brush (Andwin Scientific) and an endometrial tissue biopsy was collected for mRNA expression and histology. The first postpartum follicular growth cycle was monitored at 7, 10, 11, 13, 15, 17, 19, 21, 23, 25, 27, and 28 DIM via transrectal ultrasonography. Time to first ovulation did not differ between treatments and averaged 18 ± 1.6 DIM. Follicular diameter at first ovulation was not affected by the treatments, but the growth rate of dominant follicle before first ovulation tended to be lower for cows in POST-L in comparison with cows in POST-C. Prevalence of fetid vaginal discharge and metritis did not differ between treatments. Cows in PRE-L POST-L had lower polymorphonuclear leukocytes percentage at 15 and 28 DIM than cows in PRE-L POST-C, PRE-C POST-L, and PRE-C POST-C. Feeding RPL prepartum downregulates the expression of TLR4, SLC7A6, EHMT2, and tends to downregulate the expression of PTGES3 in uterine tissues at 28 DIM. Additionally, it upregulates the expression of APOL3 and NFKB1, and tends to upregulate the expression of AHCY and MAT2A. In conclusion, feeding RPL pre- and postpartum improved indicators of uterine immune status, but did not change days to first ovulation postpartum.

ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5).

We dedicate this manuscript in memory of a dear friend and colleague Bella Kaufman. The fifth International Consensus Symposium for Breast Cancer in Young Women (BCY5) took place virtually in October 2020, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY4 with incorporation of new evidence to inform the guidelines. Areas of research priorities as well as specificities in different geographic and minority populations were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

Rumen-protected methionine during heat stress alters mTOR, insulin signaling, and 1-carbon metabolism protein abundance in liver, and whole-blood transsulfuration pathway genes in Holstein cows.

We investigated effects of rumen-protected Met (RPM) during a heat stress (HS) challenge on (1) hepatic abundance of mTOR, insulin, and antioxidant signaling proteins, (2) enzymes in 1-carbon metabolism, and (3) innate immunity. Holstein cows (n = 32; mean ± standard deviation, 184 ± 59 d in milk) were randomly assigned to 1 of 2 environmental groups, and 1 of 2 diets [total mixed ration (TMR) with RPM (Smartamine M; 0.105% dry matter as top-dress) or TMR without (CON); n = 16/diet] in a split-plot crossover design. There were 2 periods with 2 phases. During phase 1 (9 d), all cows were in thermoneutral conditions (TN; temperature-humidity index = 60 ± 3) and fed ad libitum. During phase 2 (9 d), half the cows (n = 8/diet) were exposed to HS using electric heat blankets. The other half (n = 8/diet) remained in TN, but was pair-fed to HS counterparts. After a 14-d washout and 7-d adaptation period, the study was repeated (period 2) and environmental treatments were inverted relative to phase 2, but dietary treatments were the same. Blood was collected on d 6 of each phase 2 to measure immune function and isolate whole-blood RNA. Liver biopsies were performed at the end of each period for cystathione ß-synthase (CBS) and methionine adenosyltransferase activity, glutathione concentration, and protein abundance. Data were analyzed using PROC MIXED in SAS. Abundance of CUL3, inhibitor of antioxidant responses, tended to be downregulated by HS suggesting increased oxidative stress. Heat-shock protein 70 abundance was upregulated by HS. Phosphorylated mTOR abundance was greater overall with RPM, suggesting an increase in pathway activity. An environment × diet (E × D) effect was observed for protein kinase B (AKT), whereas there was a tendency for an interaction for phosphorylated AKT. Abundance of AKT was upregulated in CON cows during HS versus TN, this was not observed in RPM cows. For phosphorylated AKT, tissue from HS cows fed CON had greater abundance compared with all other treatments. The same effect was observed for EIF2A (translation initiation) and SLC2A4 (insulin-induced glucose uptake). An E × D effect was observed for INSR due to upregulation in CON cows during HS versus TN cows fed CON or RPM. There was an E × D effect for CBS, with lower activity in RPM versus CON cows during HS. The CON cows tended to have greater CBS during HS versus TN. An E × D effect was observed for methionine adenosyltransferase, with lower activity in RPM versus CON during HS. Although activity increased in CON during HS versus TN, RPM cows tended to have greater activity during TN. Neutrophil and monocyte oxidative burst and monocyte phagocytosis decreased with HS. An (E × D) effect was observed for whole-blood mRNA abundance of CBS, SOD1 and CSAD; RPM led to upregulation during TN versus HS. Regardless of diet, CDO1, CTH, and SOD1 decreased with HS. Although HS increased hepatic HSP70 and seemed to alter antioxidant signaling, feeding RPM may help cows maintain homeostasis in mTOR, insulin signaling, and 1-carbon metabolism. Feeding RPM also may help maintain whole-blood antioxidant response during HS, which is an important aspect of innate immune function.

Evaluation of physicochemical properties of Nile tilapia skin collagen extracted in acid médium.

Tilapia has high-temperature tolerance, can breed in captivity, grow fast, and have excellent cost-benefit. Because of these characteristics, this species is of great interest in aquaculture and, currently, the most produced fish in Brazil. However, by increasing tilapia production, there was also a rise in the amount of organic waste, mainly from filleting, which discards 70% of waste. There are many studies on collagen extraction from tilapia skin as an alternative to reduce these residues and add commercial value. In this work, the extraction of protein concentrate was tested using an acid protocol, in which the tilapia skins underwent a pre-treatment in an acid medium and saline precipitation, with variations in time and concentration. After its extraction, the skin was evaluated for ash, moisture, protein, solubility, and pH. The protein concentrate obtained showed low ash contents, and the humidity is within those presented by the literature. The protein concentrate showed levels from 68.73 to 80.58% of protein and a low solubility between 4.03 to 6.93%. In conclusion, acid extraction is a possible means of collagen extraction, and tilapia skin is a good alternative to reuse waste generated in the fish industry.

Ivermectin as a possible treatment for COVID-19: a review of the 2022 protocols.

Ivermectin is a safe and effective drug in humans and has been approved for use in numerous parasitic infections for over 50 years. In addition, many studies have already shown its antiviral activity. Ivermectin is generally well tolerated, with no indication of central nervous system-associated toxicity at doses up to 10 times the highest FDA-approved dose of 200 µg/kg. The in vitro results of ivermectin for reducing SARS-CoV-2 viral load are promising and show that Ivermectin kills SARS-CoV-2 within 48 hours. A hypothesized mechanism of action for this drug is a likely inhibition of IMPα/ß1-mediated nuclear import of viral proteins as demonstrated for other RNA viruses. However, controlled and randomized studies are needed to prove its effectiveness in COVID-19 in humans. In a single in vivo study with published results, patients confirmed to be infected with SARS-CoV-2 received at least one dose of ivermectin at any time during hospitalization. The use of ivermectin was associated with lower mortality during treatment with COVID-19, especially in patients who required increased inspired oxygen or ventilatory support. Additionally, 81 studies with the clinical use of ivermectin in humans are being carried out worldwide according to ClinicalTrials.gov. However, none of these data has been published so far. However, private and public entities in Brazil have been adopting this drug in their protocols as prophylaxis and in the initial phase of the disease. In addition, ivermectin has been used in mass treatment to prevent onchocerciasis and lymphatic filariasis in sub-Saharan Africa for many years. Surprisingly, this region has the lowest proportional mortality rate among the continents, despite the increasing numbers of infected people released by the World Health Organization.