Liver transcriptome profiles of dairy cows with different serum metabotypes.

In a previously established animal model, 38 multiparous Holstein cows were assigned to 2 groups fed different diets to achieve either a normal (NBCS) or high (HBCS) body condition score (BCS) and backfat thickness (BFT) until dry-off at -49 d before calving (NBCS: BCS <3.5 [3.02 ± 0.24) and BFT <1.2 cm [0.92 ± 0.21]; HBCS: BCS >3.75 [3.82 ± 0.33] and BFT >1.4 cm [2.36 ± 0.35], mean ± SD). The groups were also stratified for comparable milk yields (NBCS: 10,361 ± 302 kg; HBCS: 10,315 ± 437 kg; mean ± SD). The cows were then fed the same diet during the dry period and subsequent lactation, maintaining the differences in BFT and BCS throughout the study. Using the serum metabolomics data, we created a classification model that identified different metabotypes. Machine learning classifiers revealed a distinct cluster labeled HBCS-PN (HBCS predicted normal BCS) among over-conditioned cows. These cows showed higher feed intake and better energy balance than the HBCS-PH (high BCS predicted high BCS) group, while milk yield was similar. The aim of this study was to investigate the changes in the hepatic transcriptome of cows differing in serum-metabotype postpartum. We performed hepatic transcriptome analysis in cows from 3 metabolic clusters: HBCS-PH (n = 8), HBCS-PN (n = 6), and normal BCS predicted normal BCS (NBCS-PN, n = 8) on d 21 (±2) postpartum. Liver tissue from cows expressed a total of 13,118 genes aligned with the bovine genome. A total of 48 differentially expressed genes (DEG; false discovery rate ≤0.1 and fold-change >1.5) were found between NBCS-PN and HBCS-PH cows, whereas 24 DEG (14 downregulated and 10 upregulated) were found between HBCS-PN and HBCS-PH cows. The downregulated DEG (n = 31) in NBCS-PN cows compared with HBCS-PH cows are involved in biosynthetic processes such as lipid, lipoprotein, and cholesterol synthesis (e.g., APOA1, MKX, RPL3L, CANT1, CHPF, FUT1, ZNF696), cell organization, biogenesis, and localization (e.g., SLC12A8, APOA1, BRME1, RPL3L, STAG3, FBXW5, TMEM120A, SLC16A5, FGF21), catabolic processes (e.g., BREH1, MIOX, APOBEC2, FBXW5, NUDT16), and response to external stimuli (e.g., APOA1, FGF21, TMEM120A, FNDC4), whereas upregulated DEG (n = 17) are related to signal transduction and cell motility (e.g., RASSF2, ASPN, SGK1, KIF7, ZEB2, MAOA, ACKR4, TCAF1), suggesting altered metabolic adaptations during lactation. Our results showed 24 DEG between HBCS-PN and HBCS-PH in the liver. The expression of SLC12A8, SLC16A5, FBXW5, OSGIN1, LAMA3, KDELR3, OR4X17, and INHBE, which are responsible for regulating cellular processes was downregulated in HBCS-PN cows compared with HBCS-PH cows. In particular, the downregulation of SLC12A8 and SLC16A5 expression in HBCS-PN cows indicates lower metabolic load and reduced need for NAD+ biosynthesis to support mitochondrial respiratory processes. The upregulation of MAOA, ACKR4, KIF27, SFRP1, and CAV2 in the liver of HBCS-PN cows may indicate adaptive mechanisms to maintain normal liver function in response to increased metabolic demands from over-conditioning. These molecular differences underscore the existence of distinct metabolic types in cows and provide evidence for the role of the liver in shaping different metabolic patterns.

Effects of temperature-humidity index on blood metabolites of German dairy cows and their female calves.

Heat stress (HS) impairs productivity, health, and welfare in dairy cows, and additionally causes metabolic changes. Hence, specific metabolites could be used as HS biomarkers. Consequently, the aim of the present study was to compare blood metabolite concentrations of German Holstein dairy cows and of their female calves suffering from high temperature-humidity index (THI) during late gestation (cows) or during their first week of life (calves) or not. According to the mean daily THI (mTHI) at the day before blood sampling, animals were classified into 2 groups: high mTHI ≥60 (hmTHI) and low mTHI <60 (lmTHI). To perform a standard cross-sectional 2-group study, cow groups (n = 48) and calf groups (n = 47) were compared separately. Differences in metabolite concentrations between hmTHI and lmTHI animals were inferred based on a targeted metabolomics approach. In the first step, processed metabolomics data were evaluated by multivariate data analysis techniques, and were visualized using the web-based platform MetaboAnalyst V5.0. The most important metabolites with pronounced differences between groups were further analyzed in a second step using linear mixed models. We identified 9 thermally sensitive metabolites for the cows [dodecanedioic acid; 3-indolepropionic acid; sarcosine; triglycerides (14:0_34:0), (16:0_38:7), (18:0_32:1), and (18:0_36:2); phosphatidylcholine aa C38:1; and lysophosphatidylcholine a C20:3] and for the calves [phosphatidylcholines aa C38:1, ae C38:3, ae C36:0, and ae C36:2; cholesteryl esters (17:1) and (20:3); sphingomyelins C18:0 and C18:1; and p-cresol sulfate], most of them related to lipid metabolism. Apart from 2 metabolites (3-indolepropionic acid and sarcosine) in cows, the metabolite plasma concentrations were lower in hmTHI than in lmTHI groups. In our heat-stressed dry cows, results indicate an altered lipid metabolism compared with lactating heat-stressed cows, due to the missing antilipolytic effect of HS. The results also indicate alterations in lipid metabolism of calves due to high mTHI in the first week of life. From a cross-generation perspective, high mTHI directly before calving seems to reduce colostrum quality, with detrimental effects on metabolite concentrations in offspring.

Clinical Outcomes of Patients with Metastatic Breast Cancer Treated with Hypo-Fractionated Liver Radiotherapy.

PURPOSE: To retrospectively review the clinical outcomes of patients with metastatic breast cancer (MBCa) following liver directed ablative intent radiotherapy (RT). METHODS: Demographics, disease and treatment characteristics of patients with MBCa who received liver metastasis (LM) directed ablative RT between 2004-2020 were analysed. The primary outcome was local control (LC), secondary outcomes included overall survival (OS) and progression-free survival (PFS) analyzed by univariate (UVA) and multi-variable analysis (MVA). RESULTS: Thirty MBCa patients with 50 LM treated with 5-10 fraction RT were identified. Median follow-up was 14.6 (range 0.9-156.2) months. Class of metastatic disease was described as induced (12 patients, 40%), repeat (15 patients, 50%) and de novo (three patients, 10%). Median size of treated LM was 3.1 cm (range 1-8.8 cm) and median biologically effective dose delivered was 122 (Q1-Q3; 98-174) Gy3. One-year LC rate was 100%. One year and two-year survival was 89% and 63%, respectively, with size of treated LM predictive of OS (HR 1.35, p = 0.023) on UVA. Patients with induced OMD had a significantly higher rate of progression (HR 4.77, p = 0.01) on UVA, trending to significance on MVA (HR 3.23, p = 0.051). CONCLUSIONS: Hypo-fractionated ablative liver RT in patients with MBCa provides safe, tolerable treatment with excellent LC.

Abomasal infusion of essential fatty acids and conjugated linoleic acid during late pregnancy and early lactation affects immunohematological and oxidative stress markers in dairy cows.

Oxidative stress and inflammation, as natural parts of metabolic adaptations during the transition from late gestation to early lactation, are critical indicators of dairy cows' metabolic health. This study was designed to investigate the effects of abomasal infusion of essential fatty acids (EFA), particularly α-linolenic acid, and conjugated linoleic acid (CLA) on plasma, erythrocyte, and liver markers of oxidative stress in dairy cows during the transition period. Rumen-cannulated German Holstein cows (n = 38) in their second lactation (11,101 ± 1,118 kg milk/305 d, mean ± standard deviation) were abomasally infused with one of the following treatments from d -63 antepartum until d 63 postpartum (PP): CTRL (n = 9; 76 g/d coconut oil); EFA (n = 9; 78 g/d linseed plus 4 g/d safflower oil); CLA (n = 10; isomers cis-9,trans-11 and trans-10,cis-12 CLA; 38 g/d); and EFA+CLA (n = 10; 120 g/d). Hematological parameters as well as markers of oxidative status were measured in plasma, erythrocytes, and liver before and after calving. Immunohematological parameters, including erythrocyte number, hematocrit, hemoglobin, mean corpuscular hemoglobin, leukocytes, and basophils, were affected by time, and their peak levels were observed on the day after calving. The oxidative stress markers glutathione peroxidase 1 and reactive oxygen metabolites in plasma and erythrocytes were both affected by time, exhibiting the highest levels on d 1 PP, whereas ß-carotene, retinol, and tocopherol were at their lowest levels at the same time. Immunohematological parameters were only marginally affected by fatty acid treatment in a time-dependent manner. As such, lymphocyte and atypical lymphocyte counts were both significantly highest in the groups that received EFA at d 1 PP. Moreover, EFA supplementation increased the mean corpuscular volume and showed a trend for induction of mean corpuscular hemoglobin compared with the CLA group during the transition period. The PP mean thrombocyte volume was higher in the EFA than in the CLA group (except for d 28) and both EFA and CLA reduced number of thrombocytes and thrombocrit at distinct time points. Hepatic mRNA abundance of markers related to oxidative status, including glutathione peroxidase (GPX-1) and catalase (CAT), was lower (P < 0.05) in EFA-treated than non-EFA-treated cows at d 28 PP. Dairy cows at the onset of lactation were characterized by induced markers of both oxidative stress and inflammation. Supplementing EFA and CLA had minor and time-dependent effects on markers of oxidative stress in plasma, erythrocytes, and liver. A comparison of EFA supplementation with CLA or CTRL showed higher immunohematological response at d 1 PP and lower hepatic antioxidant levels by d 28 PP. Supplementation with EFA+CLA had only a minor effect on oxidative markers, which were more similar to those with the EFA treatment. Altogether, despite the time-dependent differences, the current findings show only minor effects of EFA and CLA supplementation in the prevention of early lactation-induced oxidative stress.

Comprehensive Cardiovascular Magnetic Resonance Tissue Characterization and Cardiotoxicity in Women With Breast Cancer.

Importance: There is a growing interest in understanding whether cardiovascular magnetic resonance (CMR) myocardial tissue characterization helps identify risk of cancer therapy-related cardiac dysfunction (CTRCD). Objective: To describe changes in CMR tissue biomarkers during breast cancer therapy and their association with CTRCD. Design, Setting, and Participants: This was a prospective, multicenter, cohort study of women with ERBB2 (formerly HER2)-positive breast cancer (stages I-III) who were scheduled to receive anthracycline and trastuzumab therapy with/without adjuvant radiotherapy and surgery. From November 7, 2013, to January 16, 2019, participants were recruited from 3 University of Toronto-affiliated hospitals. Data were analyzed from July 2021 to June 2022. Exposures: Sequential therapy with anthracyclines, trastuzumab, and radiation. Main Outcomes and Measures: CMR, high-sensitivity cardiac troponin I (hs-cTnI), and B-type natriuretic peptide (BNP) measurements were performed before anthracycline treatment, after anthracycline and before trastuzumab treatment, and at 3-month intervals during trastuzumab therapy. CMR included left ventricular (LV) volumes, LV ejection fraction (EF), myocardial strain, early gadolinium enhancement imaging to assess hyperemia (inflammation marker), native/postcontrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis, T2 mapping to assess edema, and late gadolinium enhancement (LGE) to assess replacement fibrosis. CTRCD was defined using the Cardiac Review and Evaluation Committee criteria. Fixed-effects models or generalized estimating equations were used in analyses. Results: Of 136 women (mean [SD] age, 51.1 [9.2] years) recruited from 2013 to 2019, 37 (27%) developed CTRCD. Compared with baseline, tissue biomarkers of myocardial hyperemia and edema peaked after anthracycline therapy or 3 months after trastuzumab initiation as demonstrated by an increase in mean (SD) relative myocardial enhancement (baseline, 46.3% [16.8%] to peak, 56.2% [18.6%]), native T1 (1012 [26] milliseconds to 1035 [28] milliseconds), T2 (51.4 [2.2] milliseconds to 52.6 [2.2] milliseconds), and ECV (25.2% [2.4%] to 26.8% [2.7%]), with P <.001 for the entire follow-up. The observed values were mostly within the normal range, and the changes were small and recovered during follow-up. No new replacement fibrosis developed. Increase in T1, T2, and/or ECV was associated with increased ventricular volumes and BNP but not hs-cTnI level. None of the CMR tissue biomarkers were associated with changes in LVEF or myocardial strain. Change in ECV was associated with concurrent and subsequent CTRCD, but there was significant overlap between patients with and without CTRCD. Conclusions and Relevance: In women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, CMR tissue biomarkers suggest inflammation and edema peaking early during therapy and were associated with ventricular remodeling and BNP elevation. However, the increases in CMR biomarkers were transient, were not associated with LVEF or myocardial strain, and were not useful in identifying traditional CTRCD risk.

Investigation of the occurrence of binder material on airborne respirable mineral wool fibers.

Mineral wool fibers can be released into the air during the production and handling of a mineral wool product where a small fraction of fibers will stay airborne and can potentially be inhaled. The aerodynamic fiber diameter determines how far an airborne fiber can pass through the human airway. Respirable fibers with an aerodynamic diameter < 3 µm can reach the deep part of the lungs (i.e., the alveolar region). Binder material (i.e., organic binder and mineral oil) is used in the production of mineral wool products. However, at the current stage, it is unknown if airborne fibers can contain binder material. We explored binder presence on airborne respirable fiber fractions being released and collected during the installation of two mineral wool products (a stone wool product and a glass wool product). Fiber collection was done by pumping a controlled air volume (2, 13, 22, and 32 l/min) through polycarbonate membrane filters during the installation of the mineral wool products. The morphological and chemical composition of the fibers were studied using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDXS) analysis. The study demonstrates that binder material is found on the surface of the respirable mineral wool fiber mainly as circular or elongated droplets. Our findings suggest that respirable fibers explored in previous epidemiological studies, which have been used for proving a lack of hazardous effects of mineral wool on humans, may have also contained binder materials on the fibers.

Growth performance and economic impact of Simmental fattening bulls fed dry or corn silage-based total mixed rations.

Bull-fattening diets in Europe and most developed countries around the world have traditionally been based on corn silage, starch-rich, and high-energy/ high-protein supplemental feeds. The impact of climate change on crop yields feed availability, and price volatility, requires new and adapted feeding strategies, including for fattening bulls. Therefore, the objective of this study was to compare the growth performance and economic impact of a representative, conventional corn silage-based (CONVL) total mixed ration, and a dry (DRY) total mixed ration (TMR) fed to Simmental bulls. For nine months (272 days), 24 bulls (215 ± 10 kg BW) were randomly assigned to one of two TMR feeding groups (n = 12 per group). The DRY-TMR was primarily characterised by the nutrient fibre source, exclusively based on straw and other by-products. The diets were formulated and balanced based on the Cornell Net Carbohydrate and Protein System. After 272 days of fattening, bulls were slaughtered. Feed intake, average daily gain (ADG)/DM intake (DMI) ratio, and nutrient intake were affected by treatment, time, and their interaction (P < 0.05). The treatment affected neither acid detergent lignin intake nor starch intake. Compared with CONVL bulls, animals fed DRY-TMR consumed more non-fibre carbohydrates and rumen undegradable neutral detergent fibre, showing lesser dry and fresh matter intake and less metabolisable energy and physically effective neutral detergent fibre intake. Despite differences in nutrient intake (P < 0.05), particle size distribution between the two diets and growth performance were not different (P = 0.45). Simmental bulls in both treatment groups reached target weight in a shorter time due to high ADG of 1.87 kg (DRY-TMR) and 1.84 kg (CONVL). Both treatments achieved a positive profit margin (598 ± 28 €/bull). While total income per bull and dressing percentage did not differ between treatments, the substantially higher feed costs (P < 0.01) of the DRY-TMR resulted in a higher (P = 0.04) income over feed cost in favour of the CONVL treatment group. Despite the higher feed cost of DRY compared with CONVL diets, the better ADG/DMI ratio (P < 0.01) of DRY-TMR contributed to lower absolute feed quantity requirements during the fattening period. Due to the positive profit margin and high ADG results, DRY-TMR solutions for fattening bulls based on straw and by-products can be considered a promising alternative feeding strategy.

Measurement and assessment of grief in a large international sample.

BACKGROUND: In 2022, the International Classification of Diseases (ICD-11) and an update of the Diagnostic Statistical Manual of Mental Disorders (DSM 5 TR) were released for implementation worldwide and now include the new Prolonged Grief Disorder (PGD). The newest definition of PGD is based on robust clinical research from the Global North yet until now has not been tested for global applicability. METHODS: The current study assesses the new PGD ICD-11 criteria in a large international sample of 1393 bereaved adults. The majority of the sample was included from the USΑ. Additionally, we conduct a sub-sample analysis to evaluate the psychometric properties, probable caseness of PGD, and differences in network structure across three regions of residency (USA, Greece-Cyprus, Turkey-Iran). RESULTS: The psychometric validity and reliability of the 33-item International Prolonged Grief Disorder Scale (IPGDS) were confirmed across the whole sample and for each regional group. Using the strict diagnostic algorithm, the probable caseness for PGD for the whole sample was 3.6 %. Probable caseness was highest for the Greece-Cyprus group (6.9 %) followed by Turkey-Iran (3.2 %) and the USA (2.8 %). Finally, the network structure of the IPGDS standard items and cultural supplement items (total of 33 items) confirmed the strong connection between central items of PGD, and revealed unique network connections within the regional groups. LIMITATIONS: Future research is encouraged to include larger sample sizes and a more systematic assessment of culture. CONCLUSION: Overall, our findings confirm the global applicability of the new ICD-11 PGD disorder definition as evaluated through the newly developed IPGDS. This scale includes culturally sensitive grief symptoms that may improve clinical precision and decision-making.

The potential of three whole blood microRNAs to predict outcome and monitor treatment response in sarcoid-bearing equids.

MicroRNAs (miRNAs) have been proposed as biomarkers for equine sarcoid (ES) disease. In this study, the suitability of three whole blood miRNAs to diagnose ES and to predict and monitor the outcome of therapy was explored. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), expression levels of eca-miR-127, eca-miR-379, and eca-miR-432 in whole blood of ES-affected equids before and at least one year after therapy were compared to those of unaffected control equids. Associations of age, sex, species, diagnosis, and therapy outcome with miRNA expression levels were examined using general linear models. In total, 48 ES-affected equids and 47 control equids were recruited. From the affected animals, 31 responded favorably to treatment, and 17 demonstrated a failure of therapy. None of the tested miRNAs were influenced by age. Male equids showed increased expression of eca-miR-127 compared to females and horses showed higher expression levels of eca-miR-379 and eca-miR-432 than donkeys. Eca-miR-127 was confirmed as a diagnostic discriminator between ES-affected and control equids. No difference in miRNA profiles before therapy was found when comparing ES-affected equids with success vs. failure of therapy. Eca-miR-379 and eca-miR-432 decreased over time in horses where therapy was successful, but not in those cases where it failed. Biological variables influence equine whole blood miRNA expression, which may complicate biomarker validation. While none of the tested miRNAs could predict the response to therapy in ES-affected equids and eca-miR-127 showed poor diagnostic accuracy for ES, eca-miR-379 and eca-miR-432 miRNAs might allow refinement of monitoring of success of ES therapy.

Representations of hallucinations and dissociation in young adult literature: using literature to challenge stigma about psychosis.

This paper explores the role that sensitively portrayed literary representations of hallucinations and dissociation may have in counteracting stigma associated with these experiences. In it, we focus on narratives of young people experiencing hallucinatory and dissociative phenomena in two award-winning, young adult novels: How It Feels to Float by Helena Fox and A Monster Calls by Patrick Ness. We identify and discuss three literary devices in these two novels that promote empathy for the characters and their experiences. The narrative accounts in both novels challenge conceptions of hallucinations and dissociation as unknowable and unrelatable experiences with their empathic portrayals of relatable characters that create comprehensible accounts of adolescents grappling with their sense of reality. Importantly, they highlight the potential role that literature can play in stigma reduction by positively shaping young peoples' understandings of unfamiliar mental health experiences.

Deep convolutional neural networks for the detection of diarrhea and respiratory disease in preweaning dairy calves using data from automated milk feeders.

The objective of the current study was to develop a predictive model for calf disease detection in the preweaning period using data from automated milk feeders (AMF). A deep convolutional neural network (CNN) architecture for the detection of respiratory disease and diarrhea in dairy calves was developed. German Holstein calves were fed milk replacer either ad libitum (up to 25 L/d; n = 32) or restrictively (6 L/d; n = 32) via AMF from 10 ± 3 d of life on. Concentrate, hay, and water were freely available. Calf health parameters were scored daily. The AMF measured milk replacer (MR) intake, number of rewarded visits, number of unrewarded visits, and drinking speed. A calf was considered sick if its fecal score was 3 or 4 and its respiratory score was 2 or 3. Only data from AMF up to 47 d of age were included in the analysis. This cut in the data was made to avoid data from the weaning period. Data were split in 80:20 ratios for training and testing data sets according to the Pareto principle. A minimum sensitivity of 80% was considered an appropriate requirement for the prediction models. Considering all calves in group housing, cross-validation of the test data set showed a sensitivity of 83% and a specificity of 79%, with a positive predictive value and a negative predictive value of 37 and 97%, respectively. The area under the curve of the receiver operating characteristic for the deep CNN model was 0.81 for all group-housed calves. The CNN model yielded sensitivity and specificity of 83 and 71%, respectively (for ad libitum-fed calves), and 82 and 87%, respectively (for restricted-fed calves), with good area under the curve-receiver operating characteristic (0.77 to 0.87), indicating that the CNN models can predict calf disease in both groups with different MR allowances. The permutation feature importance was measured by the decrease in model accuracy, and features (behaviors) were summarized in descending order of their relative importance to the CNN model. Drinking speed and MR intake were the main factors to predict calf disease in calves fed ad libitum. The number of unrewarded visits to the milk feeder and MR intake were the main factors to predict calf disease in restricted-fed calves. Despite the relatively small sample size, the results provide strong evidence that daily feeding behavior data from AMF can be used to identify calves at risk for disease. In conclusion, despite a very good testing performance of the CNN model, the relatively low daily prevalence of calf disease in the present study resulted in a high proportion of false-positive alarms.

Evaluation of the electrolyte status in hyperprolific sows on the farrowing process under different housing conditions.

In order to expand previous knowledge about the farrowing process of hyperprolific sows, the effect of calcium, magnesium and phosphor concentration in the blood and the importance of husbandry were examined. The study was performed in a small educational agriculture institution in Germany comprising 61 sows of a hyperprolific hybrid line (BHZP db.Viktoria). The sows were either kept in farrowing crates (n = 36) or pens (n = 25). Blood samples were taken every 30 min during the farrowing process, using a central venous catheter (Cavafix Certo®, 16G, 32 cm, B. Braun SE, Melsungen, Germany) placed in an ear vein. Samples for ionized calcium concentration (Caion) were analyzed directly using epoc® BGEM test cards (Alere GmbH, Cologne, Germany). Samples for total calcium (Catot), magnesium (Mg) and phosphor concentration (Pi) were deep-frozen (minus 80 °C, Innova® U202, Eppendorf SE, Hamburg, Germany) for photometric analysis at a later date. With an average farrowing duration of 267.6 ± 108.1 min (min. 71, max. 602 min), an average of 17.2 ± 4.2 piglets were born. Eutocic farrowing duration was 193.1 ± 75.2a minutes. Dystocic farrowing duration was 324.9 ± 94.1b minutes (a:b p < 0.0001). Farrowing duration did not differ between housing conditions (277.1 ± 117.4 min in crates, 275.0 ± 99.0 min in pens, p > 0.05). Dystocic farrowings were characterized by the occurrence of (at least) one time lapse of more than 60 min without piglet expulsion. In general, 35 of 61 sows suffered from dystocic parturition and received obstetrical intervention. 20 of 36 (55.6%) crate housed sows and 15 of 25 (60%) sows in pens experienced dystocic parturition (p > 0.05). Catot measured at the beginning of the expulsion stage had a prognostic value for the rest of the farrowing process. Above a threshold value of 2.385 mmol/l, eutocic parturition could be expected, while sows with a lower Catot value generally suffered from dystocic farrowings. Also, sows with eutocia had significantly higher Catot values during parturition than sows with dystocia (p = 0.001). The beginning of the lactation period was characterized by a rise in Caion (1.17 ± 0.04 to 1.21 ± 0.06 mmol/l; p < 0.0001). Mg was significantly higher before than during farrowing (p = 0.0003). During parturition, Mg decreased gradually from 0.86 ± 0.1 to 0.84 ± 0.1 mmol/l. Afterwards, Mg values showed an 18.45% increase. Sows without farrowing complications showed significantly higher Mg than those suffering from dystocia (p = 0.024). The same significant trend was observed for Pi (p = 0.002). The deficiencies in Catot/ion, Mg and Pi led to insufficient contractions and thus to farrowing problems. Parturition in the pen showed a general positive effect on the well-being of the sows and a stabilizing influence on the metabolic conditions compared to parturition in the crate. Sows in pens had higher Catot (p = 0.055) and Mg (p = 0.0004). In conclusion, the results provide clear evidence that a large proportion of hyperprolific sows suffer from previously unknown deficiencies electrolyte homeostasis around and during parturition, which is reflected by the large number of dystocic farrowings and the deficiencies in electrolyte concentrations during dystocia.

Effects of different feeding levels during a 14-week preweaning phase in dairy heifer calves on telomere length and mitochondrial DNA copy number in blood.

Telomeres cap the ends of eukaryotic chromosomes, and the telomere length (TL) is related to cellular age. The mitochondrial DNA copy number (mtDNAcn) reflects the abundance of mitochondria in a cell. In addition to generating energy, mitochondria are also the main producers of reactive oxygen species, which in turn can accelerate TL attrition and impair mitochondrial function. Nutrition in early life could influence mtDNAcn and TL in later life. In the present study, we investigated the effects of feeding different levels of milk replacer (MR) on TL shortening and energetic status by examining mtDNAcn of heifers during their first year of life. In this study, whole blood samples were obtained from German Holstein heifer calves 36 to 48 h after birth (wk 1) and at wk 12 and wk 16 of life (n = 37), as well as from 31 calves when reaching 1 yr of age. Calves were fed either a high level of MR (14% solids) at 10 L/d (1.4 kg of MR/d; n = 18) or a restrictive low level at 5.7 L/d (0.8 kg of MR/d; n = 19) until linear weaning in wk 13 to 14 of life. Additional whole blood samples were taken from their respective dams 36 to 48 h after calving. Relative TL (qT) and mtDNAcn in cells from whole blood were measured by multiplex quantitative PCR. The greatest qT values were observed in neonates (36-48 h after birth), with decreasing qT values thereafter. Delta qT values were calculated as ΔqT = qT (first year of life) - initial qT (36-48 h after birth). We found no effect of the feeding regimen on qT values, but qT decreased with age. The mtDNAcn was lowest in neonates, increased until wk 12 of life, and then remained at a constant level until after weaning (wk 16). After the first year of life, mtDNAcn was decreased and returned to levels comparable to those of the neonatal stage. No differences in mtDNAcn were detectable between feeding groups within each time point. When comparing the values of qT and mtDNAcn between the calves and their dams after calving (36-48 h after birth and after calving), greater values were observed in calves than in dams. Delta qT values were negative in all but 2 calves (on the restricted diet), indicating that the change in TL with age was not uniform among individual animals, whereas no difference in mean ΔqT values occurred between the feeding groups. Additional analyses of the correlation between qT, mtDNAcn, and various indicators of oxidative status from birth until wk 16 of life did not indicate major interactions between oxidative status, qT and mtDNAcn. The results of this study support an age-dependent decrease of TL in calves independent of the MR feeding level and show the dynamic changes of mtDNAcn in early life.

Perovskite-organic tandem solar cells with indium oxide interconnect.

Multijunction solar cells can overcome the fundamental efficiency limits of single-junction devices. The bandgap tunability of metal halide perovskite solar cells renders them attractive for multijunction architectures1. Combinations with silicon and copper indium gallium selenide (CIGS), as well as all-perovskite tandem cells, have been reported2-5. Meanwhile, narrow-gap non-fullerene acceptors have unlocked skyrocketing efficiencies for organic solar cells6,7. Organic and perovskite semiconductors are an attractive combination, sharing similar processing technologies. Currently, perovskite-organic tandems show subpar efficiencies and are limited by the low open-circuit voltage (Voc) of wide-gap perovskite cells8 and losses introduced by the interconnect between the subcells9,10. Here we demonstrate perovskite-organic tandem cells with an efficiency of 24.0 per cent (certified 23.1 per cent) and a high Voc of 2.15 volts. Optimized charge extraction layers afford perovskite subcells with an outstanding combination of high Voc and fill factor. The organic subcells provide a high external quantum efficiency in the near-infrared and, in contrast to paradigmatic concerns about limited photostability of non-fullerene cells11, show an outstanding operational stability if excitons are predominantly generated on the non-fullerene acceptor, which is the case in our tandems. The subcells are connected by an ultrathin (approximately 1.5 nanometres) metal-like indium oxide layer with unprecedented low optical/electrical losses. This work sets a milestone for perovskite-organic tandems, which outperform the best p-i-n perovskite single junctions12 and are on a par with perovskite-CIGS and all-perovskite multijunctions13.

Blood and adipose tissue steroid metabolomics and mRNA expression of steroidogenic enzymes in periparturient dairy cows differing in body condition.

In high-yielding dairy cows, the rapidly increasing milk production after parturition can result in a negative nutrient balance, since feed intake is insufficient to cover the needs for lactation. Mobilizing body reserves, mainly adipose tissue (AT), might affect steroid metabolism. We hypothesized, that cows differing in the extent of periparturient lipomobilization, will have divergent steroid profiles measured in serum and subcutaneous (sc)AT by a targeted metabolomics approach and steroidogenic enzyme profiles in scAT and liver. Fifteen weeks antepartum, 38 multiparous Holstein cows were allocated to a high (HBCS) or normal body condition (NBCS) group fed differently until week 7 antepartum to either increase (HBCS BCS: 3.8 ± 0.1 and BFT: 2.0 ± 0.1 cm; mean ± SEM) or maintain BCS (NBCS BCS: 3.0 ± 0.1 and BFT: 0.9 ± 0.1 cm). Blood samples, liver, and scAT biopsies were collected at week -7, 1, 3, and 12 relative to parturition. Greater serum concentrations of progesterone, androsterone, and aldosterone in HBCS compared to NBCS cows after parturition, might be attributed to the increased mobilization of AT. Greater glucocorticoid concentrations in scAT after parturition in NBCS cows might either influence local lipogenesis by differentiation of preadipocytes into mature adipocytes and/or inflammatory response.

A Combined Echocardiography Approach for the Diagnosis of Cancer Therapy-Related Cardiac Dysfunction in Women With Early-Stage Breast Cancer.

IMPORTANCE: Diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) remains a challenge. Cardiovascular magnetic resonance (CMR) provides accurate measurement of left ventricular ejection fraction (LVEF), but access to repeated scans is limited. OBJECTIVE: To develop a diagnostic model for CTRCD using echocardiographic LVEF and strain and biomarkers, with CMR as the reference standard. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, patients were recruited from University of Toronto-affiliated hospitals from November 2013 to January 2019 with all cardiac imaging performed at a single tertiary care center. Women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were included. The main exclusion criterion was contraindication to CMR. A total of 160 patients were recruited, 136 of whom completed the study. EXPOSURES: Sequential therapy with anthracyclines and trastuzumab. MAIN OUTCOMES AND MEASURES: Patients underwent echocardiography, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), and CMR studies preanthracycline and postanthracycline every 3 months during and after trastuzumab therapy. Echocardiographic measures included 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS). LVEF CTRCD was defined using the Cardiac Review and Evaluation Committee Criteria, GLS or GCS CTRCD as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and ≥ 35 pg/mL, respectively, at any follow-up point. Combinations of echocardiographic measures and biomarkers were examined to diagnose CMR CTRCD using conditional inference tree models. RESULTS: Among 136 women (mean [SD] age, 51.1 [9.2] years), CMR-identified CTRCD occurred in 37 (27%), and among those with analyzable images, in 30 of 131 (23%) by 2-D LVEF, 27 of 124 (22%) by 3-D LVEF, 53 of 126 (42%) by GLS, 61 of 123 (50%) by GCS, 32 of 136 (24%) by BNP, and 14 of 136 (10%) by hsTnI. In isolation, 3-D LVEF had greater sensitivity and specificity than 2-D LVEF for CMR CTRCD while GLS had greater sensitivity than 2-D or 3-D LVEF. Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for the optimal diagnosis of CTRCD (area under the receiver operating characteristic curve, 89.3%). The probability of CTRCD when results for all 3 tests were negative was 1.0%. When 3-D LVEF was replaced by 2-D LVEF in the model, the algorithm still performed well; however, its primary value was to rule out CTRCD. Biomarkers did not improve the ability to diagnose CTRCD. CONCLUSIONS AND RELEVANCE: Using CMR CTRCD as the reference standard, these data suggest that a sequential approach combining echocardiographic 3-D LVEF with 2-D GLS and 2-D GCS may provide a timely diagnosis of CTRCD during routine CTRCD surveillance with greater accuracy than using these measures individually. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02306538.

Supporting an Athlete With Breast Cancer: A Case Report.

For cancer survivors who also identify as athletes, a rigorous exercise that was once part of their daily routine and fundamental to their physical, psychological, and potentially financial well-being, may be temporarily or permanently altered in ways that exacerbate cancer-related changes in quality of life. This report presents an illustrative case of an endurance athlete who underwent breast cancer treatment and her subsequent return to high-performance, high elevation sport. We identify gaps in oncology research and patient educational tools to counsel athletes with cancer regarding the acute and long-term effects of cancer treatment and possibility of returning to a precancer level of fitness and performance. The report also highlights the need to tailor individualized cancer care treatment, rehabilitation, and the ability to preempt potential clinical and psychological side effects that may substantially impact training and competition.