Oxylipids are associated with higher disease risk in postpartum cows.

Postpartum diseases are a major animal welfare and economic concern for dairy producers. Dysregulated inflammation, which may begin as soon as the cessation of lactation, contributes to the development of postpartum diseases. The ability to regulate inflammation and mitigate postpartum health diseases relies, in part, on the production of inflammatory mediators known as oxylipids. The objective of this study was to examine associations between oxylipids and postpartum diseases. Plasma samples were collected from 16 cattle via coccygeal venipuncture at the following time points: 6 d before dry-off; dry-off (d 0); 1, 2, 6, and 12 d after dry-off; 14 ± 3 d before the expected calving date; and 7 ± 2 d after calving. After calving, cows were grouped according to if clinical disease was undetected throughout the sampling period (n = 7) or if they developed a disease postpartum (n = 9). Liquid chromatography-tandem mass spectrometry was used to analyze plasma concentrations of 63 oxylipid species. Of the 32 oxylipids detected, concentrations of 7 differed between cows with no detected disease and diseased cows throughout the sampling period. Thus, a variable oxylipid profile was demonstrated through 2 major physiological transitions of a lactation cycle. Further, the information gained from this pilot study using a small number of animals with diverse diseases from a single herd suggests that it may be possible to use oxylipids at early mammary involution to alert dairy producers of cows at risk for disease after calving. Future studies should be performed in larger populations of animals, including cows from diverse geographies and dairying styles, and focus on specific diseases to evaluate the utility of oxylipids as biomarkers. Furthermore, it is important to determine the clinical implications of variable oxylipid concentrations throughout the lactation cycle and if the oxylipid profile can be modulated to improve inflammatory outcomes.

Peripheral markers of oxidative stress in Labrador retrievers with copper-associated hepatitis.

OBJECTIVES: To evaluate biomarkers of oxidative stress in dogs with copper-associated hepatitis (CAH) as compared with healthy controls, and to evaluate if these markers correlate with hepatic copper concentrations and hepatic histopathologic features. MATERIALS AND METHODS: Prospective study. Plasma reactive metabolite concentrations, plasma antioxidant potential, and plasma and urine isoprostane concentrations were determined in Labrador retrievers with copper-associated hepatitis (n=9) as well as in breed- and sex-matched (n=9) and age- and sex-matched (n=9) healthy control populations. Possible correlations between markers of oxidative stress and hepatic histopathological features also were investigated. RESULTS: Reactive metabolites (median, range) were over twofold greater in dogs with copper-associated hepatitis (87.2 RFU/µL, 60.9 to 185.6 RFU/µL) as compared to breed- and sex-matched (38.2 RFU/µL, 22.4 to 116.8 RFU/µL) and age- and sex-matched controls (32.0 RFU/µL, 18.5 to 127.4 RFU/µL). Antioxidant potential was decreased in copper-associated hepatitis dogs (6.5 TE/µL, 5.1 to 7.7 TE/µL) as compared to breed- and sex-matched controls (8.2 TE/µL, 5.3 to 11.8 TE/µL). Both reactive metabolite concentrations and the reactive metabolite to antioxidant potential ratio were positively correlated with hepatic copper concentrations. Plasma and urine isoprostanes were variable and not significantly different between populations. CLINICAL SIGNIFICANCE: Labrador retrievers with copper-associated hepatitis have altered oxidant status. Plasma reactive metabolite concentrations and the reactive metabolite to antioxidant potential ratio could be useful biomarkers. However, neither plasma nor urine isoprostanes were useful biomarkers for copper-associated hepatitis.

Changes in bovine leukemia virus serological status and lymphocyte count between dry-off and early lactation in Michigan dairy cows.

This study addresses how the serological status of bovine leukemia virus (BLV) and lymphocyte count fluctuate from dry-off to early lactation in dairy cattle. Very few studies have investigated how BLV antibody status and lymphocyte count of cows changes longitudinally during the lactation cycle. Blood samples were collected from dairy cattle (n = 149) on 5 commercial dairy herds in Michigan at dry-off, close-up, and 7 to 10 d after calving. Plasma was analyzed for anti-BLV antibodies using a BLV-ELISA and whole blood was analyzed for lymphocyte counts. We found that BLV seroprevalence increased from dry-off (38.9%) to close-up (43.6%), then slightly decreased from close-up to 7 to 10 d after calving (43.0%). However, the change in seroprevalence was only significant from dry-off to close-up. Cows of third or higher parity were more likely to seroconvert than cows of lower parity and had the highest ELISA-negative prevalence of BLV. Lymphocyte counts were significantly higher in ELISA-positive animals, but only among second and third or greater parity animals. These results indicate that the use of lymphocyte counts as a disease severity monitoring tool for BLV should differ by parity group. Future studies should investigate if changes in seroprevalence are due to new infections or natural changes in antibody concentrations as the cow prepares for colostrum production. More accurate lymphocyte guidelines to be used for monitoring the progression of BLV should be created that consider parity and lactation stage.

Evaluation of natural plant extracts as antioxidants in a bovine in vitro model of oxidative stress.

Oxidative stress contributes to many inflammatory-based diseases of dairy cattle especially during periods of increased metabolic activity such as around calving. Endothelial cells play a key role in maintaining normal inflammatory responses, but they are especially susceptible to macromolecule damage during times of oxidative stress. Therefore, bovine aortic endothelial cells (BAEC) were used to study the effect of natural tannin-based extracts on oxidative stress that may improve health and well-being of cattle. Tannins are secondary metabolites in plants with potent antioxidant activity that have been used as natural feed additives for food-producing animals. However, there is little information on how tannin-rich plant extracts may affect oxidative stress in dairy cattle. The objective of this study was to evaluate the antioxidant effect of pomegranate (Punica granatum; PMG), tara (Caesalpinia spinosa; TA), chestnut (Castanea sativa; CH), and gambier (Uncaria gambir; GM) natural extracts using an in vitro BAEC model of oxidative stress. Natural extracts were tested at a concentration of 80 µg/mL. Viability, apoptosis, intracellular reactive oxygen species, and isoprostanes were determined on cultured BAEC treated with different plant natural extracts. No changes in cell viability was detected following PMG and GM treatments. In contrast, there was a 30% reduction of BAEC viability following treatment with CH or TA extracts. Intracellular reactive oxygen species production was significantly less abundant in cells treated with natural extracts than with the lipopolysaccharide control. Moreover, antioxidant activity varied according to the tested extract, showing a reduction of 63, 45, 51, and 27% in PMG, GM, CH, and TA, respectively. The formation of isoprostanes as a consequence of lipid peroxidation after induction of oxidative stress also were significantly decreased in PMG-treated cells when compared with the untreated cells. Theses findings suggest that PMG extract has the potential to mitigate oxidative stress without detrimental effects on cell viability. Further in vitro and in vivo research is warranted to explore the antioxidant potential of PMG extract as a dietary supplement to control oxidative stress in dairy cattle.

Serum vitamin D concentrations at dry-off and close-up predict increased postpartum urine ketone concentrations in dairy cattle.

Vitamin D is commonly supplemented to dairy cows as vitamin D3 to support calcium homeostasis and in times of low sunlight exposure. Vitamin D has beneficial immunomodulatory and anti-inflammatory properties. Serum 25-hydroxyvitamin D [25(OH)D] concentrations fluctuated during lactation, with the lowest concentrations measured in healthy cows within 7 d of calving. However, it is unknown if serum 25(OH)D concentrations measured during the previous lactation are associated with transition diseases or health risk factors in dairy cattle. We collected serum samples from 279 dairy cattle from 5 commercial dairy herds in Michigan at dry-off, close-up, and 2-10 d in milk (DIM). Vitamin D concentrations were determined by measuring serum 25(OH)D by radioimmunoassay. Total serum calcium was measured by colorimetric methods. Body condition scores (BCS) were assigned at the time of blood collection. Clinical disease incidence was monitored until 30 d postparturition. Separate bivariable logistic regression analyses were used to determine if serum 25(OH)D at dry-off, close-up, and 2-10 DIM was associated with various clinical diseases including mastitis, lameness, and uterine disorders (classified as metritis, retained placenta, or both) and increased urine ketone concentrations at P < 0.05. Among all significant bivariable analyses, multivariable logistic regression analyses were built to adjust for potential confounding variables including parity, BCS, season, and calcium. Receiver operator characteristic (ROC) curve analyses were used to determine optimal concentrations of serum 25(OH)D. We found that higher serum 25(OH)D concentrations at dry-off and close-up predicted increased urine ketone concentrations in early lactation, even after adjustment for confounders. Alternatively, we found that lower serum 25(OH)D at 2-10 DIM was associated with uterine diseases. Optimal concentrations for serum 25(OH)D at dry-off and close-up for lower risk of increased urine ketone concentrations were below 103.4 and 91.1 ng/mL, respectively. The optimal concentration for serum 25(OH)D at 2-10 DIM for uterine diseases was above 71.4 ng/mL. These results indicate that serum 25(OH)D at dry-off and close-up may be a novel predictive biomarker for increased urine ketone concentrations during early lactation. Increased urine ketone concentrations are not necessarily harmful or diagnostic for ketosis but do indicate development of negative energy balance, metabolic stress, and increased risk of early lactation diseases. Predicting that dairy cattle are at increased risk of disease facilitates implementation of intervention strategies that may lower disease incidence. Future studies should confirm these findings and determine the utility of serum 25(OH)D concentrations as a predictive biomarker for clinical and subclinical ketosis.

Cohort-level disease prediction by extrapolation of individual-level predictions in transition dairy cattle.

Dairy cattle experience metabolic stress during the transition from late gestation to early lactation resulting in higher risk for several economically important diseases (e.g. mastitis, metritis, and ketosis). Metabolic stress is described as a physiological state composed of 3 processes: nutrient metabolism, oxidative stress, and inflammation. Current strategies for monitoring transition cow nutrient metabolism include assessment of plasma non-esterified fatty acids and beta-hydroxybutyrate concentrations around the time of calving. Although this method is effective at identifying cows with higher disease risk, there is often not enough time to implement intervention strategies to prevent health disorders from occurring around the time of calving. Previously, we published predictive models for early lactation diseases at the individual cow level at dry-off. However, it is unknown if predictive probabilities from individual-level models can be aggregated to the cohort level to predict cohort-level incidence. Therefore, our objective was to test different data aggregation methods using previously published models that represented the 3 components of metabolic stress (nutrient metabolism, oxidative stress, and inflammation). We included 277 cows from five Michigan dairy herds for this prospective cohort study. On each farm, two to four calving cohorts were formed, totaling 18 cohorts. We measured biomarker data at dry-off and followed the cows until 30 days post-parturition for cohort disease incidence, which was defined as the number of cows: 1) having one or more clinical transition disease outcome, and/or 2) having an adverse health event (abortion or death of calf or cow) within each cohort. We tested three different aggregation methods that we refer to as the p-central, p-dispersion, and p-count methods. For the p-central method, we calculated the averaged predicted probability within each cohort. For the p-dispersion method, we calculated the standard deviation of the predicted probabilities within a cohort. For the p-count method, we counted the number of cows above a specified threshold of predicted probability within each cohort. We built four sets of models: one for each aggregation method and one that included all three aggregation methods (p-combined method). We found that the p-dispersion method was the only method that produced viable predictive models. However, these models tended to overestimate incidence in cohorts with low observed counts and underestimate risk in cohorts with high observed counts.

Cohort-level disease prediction using aggregate biomarker data measured at dry-off in transition dairy cattle: A proof-of-concept study.

During the transition from late gestation to early lactation, dairy cattle are at increased risk for disease. Herd-level monitoring for disease risk involves evaluating multiple factors, including food intake, cow density, and biomarkers of nutrient metabolism. Biomarkers that are measured include non-esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHB), which are usually measured in a subset of the herd (i.e. cohort). If a certain proportion of cows in the cohort are above a specific threshold for a biomarker, the cohort is considered at high risk of disease. Few previous studies have investigated other methods to aggregate individual cow-level data to the cohort level. We designed a proof-of-concept study to determine if biomarker aggregation methods may be useful to predict cohort incidence of adverse health events including 1) clinical diseases: mastitis, metritis, retained placenta, ketosis, lameness, pneumonia, milk fever, displaced abomasum, 2) and abortion or death of the calf or the cow. The study design was a prospective cohort study that used cows (N = 277) from five Michigan commercial dairy herds. Multiple cohorts of cows (two to four cohorts per farm, 18 total) were enrolled that shared the same dry-off date. We tested three different methods (central, dispersion, and count) to aggregate individual cow data (i.e. biomarkers and covariates) measured at dry-off. The central method consisted of calculating the average value of each variable within a cohort, and the dispersion method involved taking the standard deviation or mean absolute deviation about the median of each variable within a cohort. The count method consisting of counting the number of cows above a specific threshold for each variable within a cohort. We used best subsets selection to select a bouquet of candidate models for each aggregation method and averaged the predictions over the model set. We built 4 sets of Poisson regression models: one for each aggregation method and a combined model that included all three methods. We evaluated the models based on goodness-of-fit, model calibration using scoring rules, and comparison of observed versus predicted counts. The central and the combined method produced models that had good fit and model calibration. These results indicate that it may be possible to use aggregate measures to predict cohort disease incidence as early as dry-off. The next step is to test biomarker aggregation methods in studies with larger sample sizes.

Predictive models for early lactation diseases in transition dairy cattle at dry-off.

During the transition period, dairy cattle undergo tremendous metabolic and physiological changes to prepare for milk synthesis and secretion. Failure to sufficiently regulate these changes may lead to metabolic stress, which increases risk of transition diseases. Metabolic stress is defined as a physiological state consisting of 3 components: aberrant nutrient metabolism, oxidative stress, and inflammation. Current monitoring methods to detect cows experiencing metabolic stress involve measuring biomarkers for nutrient metabolism. However, these biomarkers, including non-esterified fatty acids, beta-hydroxybutyrate, and calcium are typically measured a few weeks before to a few days after calving. This is a retroactive approach, because there is little time to integrate interventions that remediate metabolic stress in the current cohort. Our objective was to determine if biomarkers of metabolic stress measured at dry-off are predictive of transition disease risk. We designed a prospective cohort study carried out on 5 Michigan dairy farms (N = 277 cows). We followed cows from dry-off to 30 days post-calving. Diseases and adverse outcomes were grouped in an aggregate outcome that included mastitis, metritis, retained placenta, ketosis, lameness, pneumonia, milk fever, displaced abomasum, abortion, and death of the calf or the cow. We used best subsets selection to select candidate models for four different sets of models: one set for each component of metabolic stress (nutrient metabolism, oxidative stress, and inflammation), and a combined model that included all 3 components. We used model averaging to obtain averaged predicted probabilities across each model set. We hypothesized that the averaged predictions from the combined model set with all 3 components of metabolic stress would be more effective at predicting disease than each individual component model set. The area under the curve estimated using receiver operator characteristic curves for the combined model set (0.93; 95% confidence interval [CI] = 0.90-0.96) was significantly higher compared with averaged predictions from the inflammation (0.87; 95% CI = 0.83-0.91), oxidative stress (0.78; 95% CI = 0.72-0.84), and nutrient metabolism (0.73; 95% CI = 0.67-0.79) model sets (p < 0.05). Our results indicate that it may be possible to detect cattle at risk for some transition diseases as early as dry-off. This has important implications for disease prevention, as earlier identification of cows at risk of health disorders will allow for earlier implementation of intervention strategies. A limitation of the current study is that we did not perform external validation. Future validation studies are needed to confirm our findings.

Oxylipid profiles of dairy cattle vary throughout the transition into early mammary gland involution.

Successful lactation in multiparous dairy cattle relies on a well-managed dry period that allows the mammary gland to remodel and regenerate between lactations. Oxylipids are potent inflammatory mediators that are capable of regulating all aspects of inflammation. Although an oxylipid profile has been documented for periparturient and lactating cattle, little work has been done to define the profile of cows in the early dry period. Therefore, our group aimed to characterize the oxylipid profile in healthy cows during the transition into early mammary gland involution. Plasma samples were collected from 10 healthy Holstein dairy cows via coccygeal venipuncture 6 d before dry-off (d -6), at dry-off (d 0), and 1 (d +1), 2 (d +2), 6 (d +6), and 12 (d +12) d after the dry-off date. Liquid chromatography-mass spectrometry was used to quantify select monounsaturated fatty acids, polyunsaturated fatty acids, and saturated fatty acids, whereas oxylipids were quantified using liquid chromatography-tandem mass spectrometry. The results of this study revealed a unique profile of pro- and anti-inflammatory oxylipids throughout the transition from late lactation into the dry period. Many compounds reached the highest concentrations of the study at d +1, d +2, or d +12, whereas others reached the lowest concentrations at d +12. The characterization of this profile allows for further understanding of the physiology of early mammary involution. Future studies should investigate how the oxylipid profile of early mammary involution may affect the health and productivity of dairy cows.

Changes in biomarkers of nutrient metabolism, inflammation, and oxidative stress in dairy cows during the transition into the early dry period.

Metabolic stress occurs in dairy cows when physiologic homeostasis is disrupted as a consequence of aberrant nutrient metabolism, chronic inflammation, and oxidative stress. Early-lactation cows that suffer from metabolic stress are susceptible to health disorders that cause significant production losses. However, there is little information regarding the occurrence and effect of metabolic stress during involution. Therefore, the purpose of this study was to investigate well-known biomarkers associated with metabolic stress in early-lactation cows at various time points during the early dry period when dairy cows also are subjected to dramatic changes in physiologic homeostasis. Our group conducted a descriptive study by collecting serum and whole-blood samples from the coccygeal vein of 29 healthy dairy cows at a commercial dairy herd. Sampling points included d -6, 0, +1, +2, +6, and +12 relative to dry-off date. Samples were used to quantify biomarkers related to nutrient metabolism, oxidative stress, and inflammation that included calcium, nonesterified fatty acids, ß-hydroxybutyrate, albumin, haptoglobin, cortisol, reactive oxygen and nitrogen species, antioxidant potential, oxidant status index, and isoprostanes. Additionally, whole-blood leukocyte differentials for total leukocyte, neutrophils, lymphocytes, eosinophils, and monocytes were analyzed. Within altered nutrient metabolism biomarkers, calcium and nonesterified fatty acid concentrations changed most from d 0 to d +2 during the sampling period. Indicators of oxidant status, such as reactive oxygen and nitrogen species, antioxidant potential, and oxidant status index, generally increased throughout the sampling period except at d +2, suggesting altered redox status throughout early involution. In contrast, isoprostane concentrations fluctuated throughout the study, demonstrating that indicators of oxidative damage occurred more sporadically during the sampling period. Therefore, many of the biomarkers associated with early-lactation metabolic stress also changed during the transition from late lactation to the early dry period, but not to the same magnitude and duration previously reported in periparturient cows. Future studies should be directed toward assessing whether the magnitude and duration of biomarker expression can affect the health and well-being of cows during the early dry period.

A comparison of drinking behavior using a harmonized methodology (Liq.In 7 ) in six countries.

PURPOSE: To assess drinking occasions (volume and type) according to consumption with food in or outside meals, and location, for six countries. METHODS: A total of 10,521 participants aged 4-65 years from Argentina, Brazil, China, Indonesia, Mexico and Uruguay completed a validated 7-day fluid intake record. For each drinking event, the volume consumed, the fluid type, the location of intake, and whether the drink was accompanied by food (meal or snack) or not, was recorded. RESULTS: Similar drinking behaviors were found in Mexico and Argentina; fluid intake during meals was 48 and 45% of total fluid intake (TFI), respectively. In Brazil (55%), Indonesia (58%) and China (66%) most fluid was consumed without food. In Uruguay, 34% of TFI was with a main meal, 31% with food between meals and 35% without food. Indonesia had the highest median (25-75th percentile) TFI; 2520 (1750-3347) mL/day, and China the lowest 1138 (818-3347) mL/day. Water was consumed with meals for 37% of Chinese and 87% of Indonesian participants, while the four Latin-American American countries showed a preference for sweet drinks; 54% in Mexico, 67% in Brazil, 55% in Argentina and 59% in Uruguay. Diversity in fluid type was noted when drinking with food between meals. Apart from China, most drinking occasions (> 75%) occurred at home. CONCLUSIONS: Three distinct drinking behaviors were identified, namely, drinking with meals, drinking as a stand-alone activity, and a type of 'grazing' (i.e., frequent drinks throughout the day) behavior. Most drinking occasions occurred at home.

Fluid intake of children, adolescents and adults in Indonesia: results of the 2016 Liq.In7 national cross-sectional survey.

PURPOSE: To report daily total fluid intake (TFI) and fluid types in Indonesia according to age, sex, socio-economic status (SES) and geographic region, and compare TFI with the Indonesian adequate fluid intake (AI) recommendations. METHODS: Data were collected in 32 cities over nine regions from children (4-9 years, n = 388), adolescents, (10-17 years, n = 478) and adults (18-65 years, n = 2778) using a fluid intake 7-day record (Liq.In7); socio-economic status was also recorded. The 7-day mean TFIs were compared with the AI of water set by the Ministry of Health of the Republic of Indonesia. RESULTS: Total median fluid intakes for all age groups exceeded 2000 mL/day. At population level, TFI was associated with household income (P < 0.001), education (P < 0.001) and Indonesian geographical regions (P < 0.001). More than 67% of participants met the AI of water from fluids. A higher percentage of children and adolescents met the AI (78 and 80%, respectively), compared with adults (72%). Drinking water was the main contributor to TFI in all age groups (76-81%). Sugar-sweetened beverages (SSB) were consumed by 62% children, 72% adolescents and 61% of adults. An SSB intake ≥ 1 serving per day was observed for 24% children, 41% adolescents and 33% adults. CONCLUSIONS: A high percentage of the population drank enough to meet the AI of water from fluids. Water was the most frequently consumed drink; however, many participants consumed at least one serving of SSB per day. This study provides data to help direct targeted intervention programs.

Fluid intake in urban China: results of the 2016 Liq.In 7 national cross-sectional surveys.

PURPOSE: To describe total fluid intake (TFI) and types of fluid consumed in urban China by age, gender, regions and city socioeconomic status relative to the adequate intakes (AI) set by the Chinese Nutrition Society. METHODS: In 2016, participants aged 4-9, 10-17 and 18-55 years were recruited via a door-to-door approach in 27 cities in China. In total, 2233 participants were included. The volumes and sources of TFI were collected using the Liq.In 7 record, assisted by a photographic booklet of standard fluid containers. RESULTS: The mean daily TFI among children, adolescents and adults were 966, 1177 and 1387 mL, respectively. In each age group, TFI was significantly higher in male vs female (981 vs 949, 1240 vs 1113, 1442 vs 1332; mL). Approximately 45, 36 and 28% of children, adolescents and adults reached the AI. Although plain water was the highest contributor to TFI, the contribution of sugar sweetened beverages (SSB) was ranked in the top three together with water and milk and derivatives. Approximately 27, 48 and 47% of children, adolescents and adults consumed more than one serving of SSB per day, respectively. CONCLUSIONS: A relatively large proportion of participants did not drink enough to meet the AI in urban China. Many children, adolescents and adults consumed more than one serving of SSB per day. A majority of children, adolescents and adults in the study population do not meet both quantitative and qualitative fluid intake requirements, and signal socioeconomic disparities.

Fluid intake of Latin American adults: results of four 2016 Liq.In7 national cross-sectional surveys.

PURPOSE: To report total fluid intake (TFI) and the intake of different fluid types in adults (≥ 18 years old) from Mexico, Argentina, Brazil and Uruguay. To compare intakes between countries and with recommended adequate intake (AI) of water from fluids. METHODS: Cross-sectional data were collected using a validated liquid intake 7-day record (Liq.In 7 ) in populations from Argentina (n = 1089), Brazil (n = 477), Mexico (n = 1677) and Uruguay (n = 554). Population characteristics, including age, gender, body mass index and socioeconomic level were recorded. Mean TFI was compared with the AI of water from fluids set by the USA Institute of Medicine. RESULTS: The lowest TFI was recorded in Mexican women (1748 mL/day) and the highest in Argentinean men (2318 mL/day). Median daily TFI was significantly different between countries; Uruguay and Argentina had higher values than Mexico and Brazil. In the former, plain water contributed to only 25% of TFI, the remainder being predominantly from hot beverages. Approximately, a third of adults did not drink enough fluid to meet the recommended AI. High SSB consumption was reported, which was significantly different between countries (p < 0.05), the highest being in Mexico (median 25-75th percentiles): 531 (300-895 mL/day. CONCLUSIONS: This survey highlights the need to increase water consumption and reduce SSB intake in this region to avoid potential associated health risks. These findings may be useful information in monitoring public health policy strategies.

Fluid intake of Latin American children and adolescents: results of four 2016 LIQ.IN 7 National Cross-Sectional Surveys.

PURPOSE: The primary aim of this survey was to report total fluid intake (TFI) and different fluid types for children (4-9 years) and adolescents (10-17 years) in Mexico, Brazil, Argentina and Uruguay. The second aim was to compare TFI with the adequate intake (AI) of water from fluids as recommended by the USA Institute of Medicine. METHODS: Data were collected using a validated liquid intake 7-day record (Liq.In 7 ). Participants' characteristics, including age, sex and anthropometric measurements were recorded. RESULTS: A total of 733 children and 933 adolescents were recruited. Over 75% of children in Uruguay met the IOM's recommended intake. Fewer children in Argentina (64-72%) and Brazil (41-50%) obtained AI and the lowest values were recorded in Mexico (33-44%), where 16% of boys and 14% girls drank 50% or less of the AI. More adolescents in Argentina (42%) met the AIs than other countries; the lowest was in Mexico (28%). Children and adolescents in Mexico and Argentina drank more sugar sweetened beverages than water. CONCLUSIONS: Large numbers of children and adolescents did not meet AI recommendations for TFI, raising concerns about their hydration status and potential effects on mental and physical well-being. Given the negative effects on children's health, the levels of SSB consumption are worrying.

Fluid intake patterns of children and adolescents: results of six Liq.In7 national cross-sectional surveys.

PURPOSE: This study aimed to identify and characterize patterns of fluid intake in children and adolescents from six countries: Argentina, Brazil, China, Indonesia, Mexico and Uruguay. METHODS: Data on fluid intake volume and type amongst children (4-9 years; N = 1400) and adolescents (10-17 years; N = 1781) were collected using the validated 7-day fluid-specific record (Liq.In7 record). To identify relatively distinct clusters of subjects based on eight fluid types (water, milk and its derivatives, hot beverages, sugar-sweetened beverages (SSB), 100% fruit juices, artificial/non-nutritive sweetened beverages, alcoholic beverages, other beverages), a cluster analysis (partitioning around k-medoids algorithm) was used. Clusters were then characterized according to their socio-demographics and lifestyle indicators. RESULTS: The six interpretable clusters identified were: low drinkers-SSB (n 523), low drinkers-water and milk (n 615), medium mixed drinkers (n 914), high drinkers-SSB (n 513), high drinkers-water (n 352) and very high drinkers-water (n 264). Country of residence was the dominant characteristic, followed by socioeconomic level, in all six patterns. CONCLUSIONS: This analysis showed that consumption of water and SSB were the primary drivers of the clusters. In addition to country, socio-demographic and lifestyle factors played a role in determining the characteristics of each cluster. This information highlights the need to target interventions in particular populations aimed at changing fluid intake behavior and improving health in children and adolescents.

Reduced serum vitamin D concentrations in healthy early-lactation dairy cattle.

Cattle obtain vitamin D by ingestion or cutaneous exposure to UV light. Dairy cattle diets are frequently supplemented with vitamin D to compensate for limited sun exposure or during times of increased metabolic demands, such as the periparturient period, to maintain calcium homeostasis. Whether housing and supplemental vitamin D practices supply adequate amounts of vitamin D to optimally support the transition from gestation to lactation in dairy cattle is unknown. Our objective was to determine how serum vitamin D concentrations of dairy cows change with season, age, parity, and stage of lactation. Clinically healthy cows (n = 183) from 5 commercial dairies were enrolled in the study. Serum samples were collected at dry off, within 7 d of entering the close-up group, and within 7 d after calving (calving+7). Vitamin D status was determined by measuring serum 25-hydroxyvitamin D [25(OH)D] by radioimmunoassay. We performed repeated-measures mixed-effects linear regression to determine the effects of season, age, parity, and lactation stage (dry off, close-up, and calving+7) on 25(OH)D concentrations in serum. Bivariable analysis indicated that parity, age, and season were not associated with serum 25(OH)D concentrations. Sample period affected 25(OH)D concentrations, with the highest 25(OH)D levels at dry off (99.7 ± 1.9 ng/mL) followed by close up (93.8 ± 2.1 ng/mL), with the lowest levels at calving+7 (82.6 ± 1.7 ng/mL). These data showed a large depletion of 25(OH)D in dairy cattle postpartum compared with late prepartum, although the biological significance of this change in these healthy cattle is unclear. Consumption of serum 25(OH)D by immune system functions and calcium homeostasis in early lactation likely caused the reduction in serum 25(OH)D concentrations after calving. These results suggest that determining whether serum 25(OH)D concentrations are associated with the incidence of transition period disease is an appropriate next step. Assessing the effects of enhanced vitamin D supplementation of cows in early lactation on postpartum diseases may be warranted.

Secukinumab in the Treatment of Psoriasis and Psoriatic Arthritis: A Review of the Literature.

While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.

Injectable chondroplasty: Enzymatic reshaping of cartilage grafts.

OBJECTIVE/HYPOTHESIS: To develop an injection-based enzymatic technique that selectively softens cartilage tissue for reshaping cartilaginous structures in the head and neck. MATERIALS AND METHODS: Two groups were formed using fresh rabbit ears: (1) whole rabbit ear group; (2) composite graft group (2.5mm×3.0cm specimens sectioned from the central region of the pinna). Subperichondrial injections using three enzymes (hyaluronidase, pronase, and collagenase II) in sequence were performed for the experimental specimens from both groups. In the control specimens, phosphate buffered saline was injected in a similar fashion. The whole ear specimens were then photographed while held upright in the anatomical vertical position to evaluate for buckling, which corresponds to the integrity of the cartilage. In addition, backlight photography was performed for all specimens to further evaluate the effect of the enzymes, such that increased light intensity represents increased cartilage digestion. RESULTS: The application of the digestive enzymes resulted in marked reduction of cartilage tissue matrix resiliency, while preserving overlying skin layers. Enzymatically treated whole pinnae buckled at the site where enzymes were delivered. Backlit images revealed increased local light intensity at the regions of digestion. There was no obvious destruction of the overlying skin upon visual inspection. CONCLUSIONS: This study demonstrates the feasibility of injectable chondroplasty as a potential alternative method to conventional surgery for auricular cartilage reshaping. Sequential injection of hyaluronidase, pronase, and collagenase II into the subperichondrial space can be performed to digest and soften cartilage structure with minimal involvement of surrounding tissue. Future studies will need to include chondrocyte viability testing and optimization of delivery techniques.

Hydration education: developing, piloting and evaluating a hydration education package for general practitioners.

OBJECTIVES: To (1) assess the hydration knowledge, attitudes and practices (KAP) of doctors; (2) develop an evidence-based training package; and (3) evaluate the impact of the training package. DESIGN: Educational intervention with impact evaluation. SETTING: Cambridgeshire, UK. PARTICIPANTS: General practitioners (GPs (primary care physicians)). INTERVENTIONS: Hydration and healthcare training. MAIN OUTCOME MEASURES: Hydration KAP score before and immediately after the training session. RESULTS: Knowledge gaps of doctors identified before the teaching were the definition of dehydration, European Food Safety Authority water intake recommendations, water content of the human body and proportion of water from food and drink. A face-to-face teaching package was developed on findings from the KAP survey and literature search. 54 questionnaires were completed before and immediately after two training sessions with GPs. Following the training, total hydration KAP scores increased significantly (p<0.001; median (25th, 75th centiles); 32 (29, 34)). Attendees rated the session as excellent or good (90%) and reported the training was likely to influence their professional practice (100%). CONCLUSIONS: The training package will continue to be developed and adapted, with increased focus on follow-up strategies as well as integration into medical curricula and standards of practice. However, further research is required in the area of hydration care to allow policymakers to incorporate hydration awareness and care with greater precision in local and national policies.