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Thanks to improvements in genetics, nutrition, and management, modern dairy cows can still produce large amounts of milk at the end of lactation, with possible negative effects on health and welfare, particularly when milking is stopped abruptly. To limit yield at dry-off, strategies involving different types of dietary restriction have been used worldwide. Thus, we aimed to investigate the effects of a reduced nutrient density at dry-off on milk production, metabolism, the pattern of rumen fermentation, and milk fatty acid profile around dry-off and in the ensuing periparturient period. During the last week before dry-off, 26 Holstein cows were enrolled in pairs according to the expected calving date and either fed ad libitum ryegrass hay (nutrient restricted, NR; 13 cows) or continued to receive lactation diet (control group, CTR; 13 cows). After dry-off, both groups received only grass hay for 7 d, and free access to water was always provided. Blood, milk, and rumen fluid samples were collected from 7 d before dry-off to 28 DIM. Milk production, DMI (during the periparturient period), and rumination times were recorded daily. At dry-off, NR cows had decreased milk yield (-62%) and milk lactose compared with CTR but had higher fat and protein contents. In the subsequent lactation, no significant differences were observed in milk yield and composition. The BCS did not differ between groups during the transition period, but it decreased in NR after dry-off. Before dry-off, NR had decreased glucose, urea, and insulin, but higher creatinine, BHB, and nonesterified fatty acids (NEFA). The day after dry-off, NEFA were lower in NR, but they were higher 7 d after calving. At dry-off, NR had higher rumen pH, lower lactate, urea, and total volatile fatty acid concentrations. Considering volatile fatty acid molar proportions, NR had increased acetate but decreased propionate and butyrate at dry-off. Rumination time dropped 6 d before dry-off in NR and after dry-off in CTR, b

Dairy cow longevity is an important economic trait for producers. In modern dairy farming, longevity of dairy cows is the result of culling decisions, which are determined by several risk factors, including diseases, and reproductive and productive performance. Previous studies have documented that seasonal changes affect health, behavior, and performance of dairy cows throughout their life cycle. Increasing cow comfort by making management adjustments to decrease exposure to high temperatures during the hot months gives farmers the opportunity to decrease culling risk factors and possibly increase cow productive life. In the present study, we obtained the records of primiparous and multiparous Holstein cows from Florida (n = 10,812) and California (n = 8,197) during a 10-yr period (2012–2022). We analyzed the relationship between birth season and longevity (i.e., cows that remained in the herd for 5 or more lactations) in Florida (n = 1,567) and in California (n = 1,669). The number of cows dead, sold, the reasons why they were sold, and their relationship with birth season were also analyzed in the Florida dataset. The hypothesis was that birth in a cool season will increase the length of herd productive life and decrease the number of cows sold or dead during all lactations. The birth seasons were cool (CL; cows born in December, January, February, or March) and hot (HS; cows born in June, July, August, or September). Results showed that in Florida, most cows that remained in the herd for more than 5 lactations (i.e., 14.5% of total cow records) were born during CL compared with cows born during HS (1,129, 72% vs. 438, 28%). The same observations were made in California, where greater longevity (i.e., 5 or more lactations, representing 20.4% of total cow records) was attributed to cows born in CL compared with HS cows (939, 56.3% vs. 730, 43.7%). In Florida, a greater number of HS were sold compared with CL cows (765, 52.6% vs. 689, 47.4%). More HS cows were sold

Controlling the properties of mid- and far-infrared radiation can provide a means to transiently alter the properties of materials for novel applications. However, a limited number of optical elements are available to control its polarization state. Here we show that a 15-µm thick liquid crystal cell containing 8CB (4-octyl-4′-cyanobiphenyl) in the ordered, smectic A phase can be used as a phase retarder or wave plate. This was tested using the bright, short-pulsed (∼1 ps) radiation centered at 16.5 µm (18.15 THz) that is emitted by a free electron laser at high repetition rate (13 MHz). These results demonstrate a possible tool for the exploration of the mid- and far-infrared range and could be used to develop novel metamaterials or extend multidimensional spectroscopy to this portion of the electromagnetic spectrum.

Dairy goat's lactation persistence forces farmers at limiting nutrient supply to reduce yield at dry-off. Omitting dry period could be a solution, but metabolic effects of this practice have never been tested. Eight Alpine (AL) and 12 Saanen (SA) goats approaching their second kidding blocked by breed and number of kids carried (single - SIN - or double - DOU) were allocated to one out of two groups (4 AL and 6 SA; 5 SIN and 5 DOU in each group). At -42 +/- 7 days from kidding (DFK), they were either dried off (DR) or milked continuously until kidding (CL). Body condition score (BCS) was assessed, and blood samples were collected at -10, -3, 5, 12, and 29 DFK to determine metabolic profile. Milk yield and composition were assessed at -56, 7, 31, 62, and 97 DFK. Compared with DR, CL had higher plasma reactive oxygen metabolites and liver enzymes. Compared with DR counterparts, AL-CL had higher nonesterified fatty acids (NEFA) at -10, whereas SA-CL had lower NEFA at -3 DFK. CL goats had lower BCS, higher plasma beta-hydroxybutyrate (BHB) and urea before kidding, but higher glucose at -3 and 5, lower NEFA at 5 and 12, and higher BCS at 29 DFK. CL goats had lower haptoglobin and myeloperoxidase at -3 and 5 DFK, paired with higher albumin, cholesterol, and paraoxonase at 12 DFK. Omitting dry period mitigated the inflammatory condition around kidding in dairy goats, possibly accounting for an improved energy balance in early lactation, despite body reserve mobilisation prepartum was greater under continuous lactation.Omitting dry period accrued prepartum energy deficit in dairy goats but improved their postpartum energy balance.Omitting dry period mitigated acute phase response and inflammation in dairy goats during the late gestation and early lactation phases.Omitting dry period in high-yielding goats could allow for a smoother transition to the new lactation coping with the limitations hindering the dry-off procedures.

The aim of this study was to investigate the associations between subclinical intramammary infection (IMI) from different pathogens combined with inflammation status and a set of blood biochemical traits including energy-related metabolites, indicators of liver function or hepatic damage, oxidative stress, inflammation, innate immunity, and mineral status in 349 lactating Holstein cows. Data were analyzed with a linear model including the following fixed class effects: days in milk, parity, herd, somatic cell count (SCC), bacteriological status (positive and negative), and the SCC x bacteriological status interaction. Several metabolites had significant associations with subclinical IMI or SCC. Increased SCC was associated with a linear decrease in cholesterol concentrations which ranged from -2% for the class >= 50,000 and < 200,000 cells/mL to -11% for the SCC class >= 400,000 cells/mL compared with the SCC class < 50,000 cells/mL. A positive bacteriological result was associated with an increase in bilirubin (+24%), paraoxonase (+11%), the ratio paraoxonase/ cholesterol (+9%), and advanced oxidation protein product concentration (+23%). Increased SCC were associated with a linear decrease in ferric reducing antioxidant power concentrations ranging from -3% for the class >= 50,000 and < 200,000 cells/mL to -9% for the SCC class >= 400,000 cells/mL (respect to the SCC class < 50,000 cells/mL). A positive bacteriological result was associated with an increase in haptoglobin concentrations (+19%). Increased SCC were also associated with a linear increase in haptoglobin concentrations, which ranged from +24% for the class >= 50,000 and < 200,000 cells/mL (0.31 g/L) to +82% for the SCC class >= 400,000 cells/mL (0.45 g/L), with respect to the SCC class < 50,000 cells/mL (0.25 g/L). Increased SCC were associated with a linear increase in ceruloplasmin concentrations (+15% for SCC >= 50,000 cells/mL). The observed changes in blood b

The cessation of lactation (i.e., dry-off) in dairy cattle is an area of research that has received much focus in recent years. The dry period is necessary to optimize tissue remodeling of the mammary gland, but repre-sents a stressful event, incorporating several changes in daily routine, diet, and metabolism. Moreover, the high milk yields achieved by modern cows in late gestation exacerbate the need for relevant manipulations in the days around dry-off, as excessive accumulation of milk might jeopardize the success of the dry period, with potential negative effects on future lactation. Produc-tion levels over 15 kg/d are an additional risk factor for udder health, delay mammary involution, and worsen metabolic stress and inflammatory responses. Furthermore, the pressure to reduce antibiotic usage in farm animals has resulted in increased attention on the dry period, given that historically most dairy cattle were provided prophylactic intramammary antibiotic treatment at dry-off as a means to reduce the risk of intramammary infections in the subsequent lactation. Several strategies have been proposed over the years to cope with these challenges, aiming to gradually reduce milk yield before dry-off, promoting at the same time the start of mammary involution. Among them, the most common are based on feed or nutrient restric-tion, a decrease in milking frequency, or administration of prolactin inhibitors. These practices have differ-ent capacities to reduce milk yield through different mechanisms and entail several implications for udder health, animal welfare, behavior, endocrine status, metabolism, and inflammatory conditions. The present review aims to provide a comprehensive overview of the dry-off phase in high-yielding cows and of the impact of high milk production at dry-off, and to describe pos-sible strategies that might be implemented by farmers and veterinarians to optimize this critical phase in an integrated way.

Positive effects have been observed as a result of Aloe arborescens supplementation in the dry-off phase in dairy cows. Metabolomic approaches can provide additional information about animal physiology. Thus, we characterized plasma metabolome around dry-off in 12 cows supplemented (AL) or not (CTR) with 10 g/d of lyophilized A. arborescens with an untargeted metabolomic approach. Overall, 1658 mass features were annotated. Regardless of treatment, multivariate statistics discriminated samples taken before and after dry-off. Overall, 490 metabolites were different between late lactation and early dry period, of which 237 were shared between AL and CTR. The most discriminant compounds (pentosidine and luteolin 7-O-glucoside) were related to the more fibrous diet. Pathway analysis indicated that pyrimidine and glycerophospholipid metabolisms were down-accumulated, suggesting reduced rumen microbial activity and liver load. Samples from AL were discriminated from CTR either the day of dry-off or 7 days after. At dry-off, aloin and emodin were the most discriminant metabolites, indicating that Aloe's bioactive compounds were absorbed. Seven days later, 534 compounds were different between groups, and emodin was among the most impacted. Pathway analysis highlighted that glycerophospholipid, pyrimidine, and folate metabolisms were affected. These results might indicate that Aloe has positive effects on liver function and a modulatory effect on rumen fermentation.

Twelve Holstein (HOL), 9 Brown Swiss (BRO), and 9 Simmental (SIM) dairy cows raised in the same barn and managed identically were enrolled to characterise the responses to the transition period. From -21 to 28 d from calving (DFC), body condition score (BCS) and milk yield were measured, and blood samples were collected to assess plasma biomarkers of metabolism, minerals, liver function, inflammation, and oxidative status. Compared with SIM, HOL and BRO had higher milk yield during the first week of lactation. HOL had the highest milk yield from the second to the fourth week and the lowest BCS at 28 DFC. SIM had the highest BCS and the highest plasma creatinine and P, reflecting a greater attitude to gain muscle mass. Compared with SIM, BRO and HOL had lower plasma fructosamine, indicating reduced glucose availability driven by lactose synthesis. SIM had the mildest acute phase response at the onset of lactation, as suggested by the lowest ceruloplasmin concentration. HOL had the highest cholesterol and paraoxonase concentrations, and the greatest interleukin-1 beta production by leukocytes following ex-vivo stimulation, suggesting that they had the quickest resolution of the acute phase response due to the fastest immune cell activation. BRO had the highest concentration of reactive oxygen metabolites, ceruloplasmin, bilirubin, glutamate-oxaloacetate transaminase, gamma-glutamyl transferase, and beta-hydroxybutyrate, and the lowest concentration of paraoxonase, reflecting the strongest activation of leukocytes and the most severe acute phase response. Together, these results highlight different metabolic and inflammatory conditions around calving in the three explored breeds.

Huge differences exist between cow yields and body sizes during their first and second lactations. The tran-sition period is the most critical and investigated phase of the lactation cycle. We compared metabolic and endocrine responses between cows at different parities during the transition period and early lactation. Eight Holstein dairy cows were monitored at their first and second calving during which they were reared under the same conditions. Milk yield, dry matter intake (DMI), and body weight (BW) were regularly measured, and energy balance, efficiency, and lactation curves were calculated. Blood samples were collected on scheduled days from -21 d relative to calving (DRC) to 120 DRC for the assessment of metabolic and hormonal profiles (biomarkers of metabolism, mineral status, inflamma-tion, and liver function). Large variations in the period in question for almost all variables investigated were observed. Compared with their first lactation, cows during their second lactation had higher DMI (+15%) and BW (+13%), their milk yield was greater (+26%), lactation peak was higher and earlier (36.6 kg/d at 48.8 DRC vs. 45.0 kg/d at 62.9 DRC), but persistency was reduced. Milk fat, protein, and lactose contents were higher during the first lactation and coagulation prop-erties were better (higher titratable acidity, faster and firmer curd formation). Postpartum negative energy balance was more severe the during the second lacta-tion (1.4-fold at 7 DRC) and plasma glucose was lower. Circulating insulin and insulin-like growth factor-1 were lower in second-calving cows during the transi-tion period. At the same time, markers of body reserve mobilization (beta-hydroxybutyrate and urea) increased. Moreover, albumin, cholesterol, and gamma-glutamyl trans-ferase were higher during second lactation, whereas bilirubin and alkaline phosphatase were lower. The inflammatory response after calving was not different, as suggested by the similar haptoglobin concentrations and

Anticoagulants, such as ethylenediaminetetraacetic acid (EDTA), sodium citrate (Na-citrate), or heparin are normally used in hematological clinical tests to prevent coagulation. Although anticoagulants are fundamental for the correct application of clinical tests, they produce adverse effects in different fields, such as those involving specific molecular techniques; for instance, quantitative real time polymerase chain reactions (qPCR) and gene expression evaluation. For this reason, the aim of this study was to evaluate the expression of 14 genes in leukocytes that were isolated from the blood of Holstein cows, and which were collected in Li-heparin, K-EDTA, or Na-citrate tubes; then, they were analyzed using qPCR. Only the SDHA gene showed a significant dependence (p ≤ 0.05) on the anticoagulant that was used with the lowest expression; this was observed in Na-Citrate after being compared with Li-heparin and K-EDTA (p < 0.05). Although a variation in transcript abundance with the three anticoagulants was observed in almost all the investigated genes, the relative abundance levels were not statistically significant. In conclusion, the qPCR results were not influenced by the presence of the anticoagulant; thus, we had the opportunity to choose the test tube that was used in the experiment without interfering effects impacting the gene expression levels caused by the anticoagulant.

The dry-off of dairy cows represents an important phase of the lactation cycle, influencing the outcome of the next lactation. Among the physiological changes, the severity of the inflammatory response can vary after the dry-off, and this response might have consequences on cow adaptation in the transition period. The plasma protein profile is a diagnostic tool widely used in humans and animals to assess the inflammatory status and predict the outcome of severe diseases. The albumin-to-globulin ratio (AG) can represent a simple and useful proxy for the inflammatory condition. In this study, we investigated the relationship between AG before dry-off and inflammation, metabolic profile, and performance of 75 Holstein dairy cows. Blood samples were collected from −62 (7 d before dry-off) to 28 d relative to calving (DFC) to measure metabolic profile biomarkers, inflammatory variables, and liver function. Daily milk yield in the first month of lactation was recorded. Milk composition, body condition score, fertility, and health status were also assessed. The AG calculated 1 wk before dry-off (−62 DFC) was used to retrospectively group cows into tertiles (1.06 ± 0.09 for HI, 0.88 ± 0.04 for IN, and 0.72 ± 0.08 for LO). Data were subjected to ANOVA using the PROC MIXED program in SAS software. Differences among groups observed at −62 DFC were almost maintained throughout the period of interest, but AG peaked before calving. According to the level of acute-phase proteins (haptoglobin, ceruloplasmin, albumin, cholesterol, retinol-binding protein), bilirubin, and paraoxonase, a generally overall lower inflammatory condition was found in HI and IN than in the LO group immediately after the dry-off but also after calving. The HI cows had greater milk yield than LO cows, but no differences were observed in milk composition. The somatic cell count reflected the AG ratio trend, with higher values in LO than IN and HI either before dry-off or after calving. Fertility was better in

The final weeks of gestation represent a critical period for dairy cows that can determine the success of the subsequent lactation. Many physiological changes take place and additional exogenous stressors can alter the success of the transition into lactation. Moreover, this phase is pivotal for the final stage of intrauterine development of the fetus, which can have negative long-lasting postnatal effects. Heat stress is widely recognised as a threat to dairy cattle welfare, health, and productivity. Specifically, late gestation heat stress impairs the dam's productivity by undermining mammary gland remodelling during the dry period and altering metabolic and immune responses in early lactation. Heat stress also affects placental development and function, with relevant consequences on fetal development and programming. In utero heat stressed newborns have reduced birth weight, growth, and compromised passive immune transfer. Moreover, the liver and mammary DNA of in utero heat stressed calves show a clear divergence in the pattern of methylation relative to that of in utero cooled calves. These alterations in gene regulation might result in depressed immune function, as well as altered thermoregulation, hepatic metabolism, and mammary development jeopardising their survival in the herd and productivity. Furthermore, late gestation heat stress appears to exert multigenerational effects, influencing milk yield and survival up to the third generation.

Simple Summary Weaning plays a vital role in the management strategy of a dairy farms, also affecting the future animals' performances, such as growth, reproduction, and lactation. At the same time weaning strategy, as days at weaning, influences the feeding cost as milk supply during the pre-weaning period reaches 40% of the total feed costs. The aim of the study was to investigate the effects of weaning age, conventional (60 days) or early (45 days) on growth performances and inflammometabolic status of ten Simmental calves. The proposed results showed how early weaning strategy seemed to not affect inflammatory status and liver functionality after weaning, highlighting the possibility to reduce rearing costs but not jeopardizing calf development, as long as calves can reach body gains as reported in the present study. At least for performance, we are aware that the low number of calves enrolled in each treatment can limit the recommendations based on our findings. Hence, this study should be considered more like an explorative investigation since no recent data are available for Simmental calves in terms of growth performance and inflammometabolic adaptation. Weaning plays a key role in health status and future performance of calves. The aim of this study was to investigate the effects of weaning age (Wa), early (45 d, EW) or conventional (60 d, CW), on growth performance and metabolic profile of ten Simmental calves (5 EW and 5 CW calves). Daily intake of milk and calf starter was recorded. Blood samples and measurements of body weight (BW), heart girth (HG), and wither height (WH) were collected at -25, -15, 0, 6, and 20 days relative to weaning. Growth performances (BW, HG, WH) were affected by Wa, resulting lower in EW calves compared with CW calves (p < 0.05). Average daily gain was affected by overall Wa and Time but also by the interaction Wa x Time (p < 0.05). EW calves had lower paraoxonase and higher oxidation protein products levels, lower glucos

Behavioral effects of non-invasive brain stimulation techniques (NIBS) can dramatically change as a function of different factors (e.g., stimulation intensity, timing of stimulation). In this framework, lately there has been a growing interest toward the importance of considering the inter-individual differences in baseline performance and how they are related with behavioral NIBS effects. However, assessing how baseline performance level is associated with behavioral effects of brain stimulation techniques raises up crucial methodological issues. How can we test whether the performance at baseline is predictive of the effects of NIBS, when NIBS effects themselves are estimated with reference to baseline performance? In this perspective article, we discuss the limitations connected to widely used strategies for the analysis of the association between baseline value and NIBS effects, and review solutions to properly address this type of question.

An unsupervised machine learning approach (ML) of rumination time (RT) data was used to evaluate metabolic and lactation performance in a cohort of Simmental dairy cows (29) around parturition. The k-means clustering (unsupervised ML) was used to generate clusters based on RT (Hr-Tags; SCR by Allflex) over 24 h from 1 to 7-d post-calving. Two large clusters were obtained: high (High-RT, n = 13) and low (Low-RT, n = 12). Milk production was recorded until 42 d in lactation and milk samples collected weekly. Blood samples were collected from −21 to +28 d relative to calving. Data were subjected to PROC MIXED of SAS. Compared with Low-RT, High-RT cows had lower plasma BHB (3, 7, and 14 d), haptoglobin (3 and 7 d), and non-esterified fatty acids (1 and 3 d). High-RT cows had greater tocopherol from 3 to 28 d, fructosamine and albumin at 7 d, and retinol at 3 and 7 d after calving than Low-RT cows. Compared with multiparous Low-RT, milk production was greater in multiparous High-RT cows, but no differences were detected for primiparous. Only for multiparous, High-RT cows displayed a greater LFI than Low-Rt cows. The close relationship between RT and the physiological state at the onset of lactation supports the use of RT as an indicator of metabolic and inflammatory adaptations to the negative energy balance of cows after parturition. At the farm level, these outcomes provide information to farmers that can be helpful in management decisions for cow health, complementing traditional methods.HIGHLIGHTS The unsupervised ML applied was able to group cows with different RT increase rates after calving based on differences in plasma biomarkers of energy metabolism, inflammatory response, and liver functionality, particularly in multiparous cows. A quicker increase in RT after calving was associated with a lower inflammatory response, lower lipid mobilisation, and greater milk production. At the farm level, the fine-tuning of specific algorithm in the actual sensors considerin

Recent research on the transition period (TP) of dairy cows has highlighted the pivotal role of immune function in affecting the severity of metabolic challenges the animals face when approaching calving. This suggests that the immune system may play a role in the etiology of metabolic diseases occurring in early lactation. Several studies have indicated that the roots of immune dysfunctions could sink way before the “classical” TP (e.g., 3 weeks before and 3 weeks after calving), extending the time frame deemed as “risky” for the development of early lactation disorders at the period around the dry-off. Several distressing events occurring during the TP (i.e., dietary changes, heat stress) can boost the severity of pre-existing immune dysfunctions and metabolic changes that physiologically affect this phase of the lactation cycle, further increasing the likelihood of developing diseases. Based on this background, several operational and nutritional strategies could be adopted to minimize the detrimental effects of immune dysfunctions on the adaptation of dairy cows to the new lactation. A suitable environment (i.e., optimal welfare) and a balanced diet (which guarantees optimal nutrient partitioning to improve immune functions in cow and calf) are key aspects to consider when aiming to minimize TP challenges at the herd level. Furthermore, several prognostic behavioral and physiological indicators could help in identifying subjects that are more likely to undergo a “bad transition”, allowing prompt intervention through specific modulatory treatments. Recent genomic advances in understanding the linkage between metabolic disorders and the genotype of dairy cows suggest that genetic breeding programs aimed at improving dairy cows’ adaptation to the new lactation challenges (i.e., through increasing immune system efficiency or resilience against metabolic disorders) could be expected in the future. Despite these encouraging steps forward in understanding the physiolog

Dairy cows at dry-off undergo several management and physiological changes, resulting in alterations in plasma biomarkers of inflammation, oxidative stress, and immune system. High milk yield at the end of lactation exacerbates these responses. The underlying mechanism of these changes has yet to be elucidated. We hypothesized altered leukocyte gene expression after dry-off and different responses in cows with different milk yield. Thirteen Holstein dairy cows were sampled at the turn of dry-off to investigated whole blood leukocyte gene expression and were grouped according to the average milk yield during the last week of lactation: low (< 15 kg/d) and high milk yield (> 15 kg/d). Blood samples were collected in PAXgene tubes (Preanalytix, Hombrechtikon, Switzerland) at -7, 7, and 34 days from dry-off (DFD) to measure mRNA abundance of 37 genes. Normalized gene abundance data were subjected to MIXED model ANOVA (SAS Institute Inc., Cary, NC). Compared with -7 DFD, at 7 DFD RNA abundance of lipoxygenase genes (ALOX5, ALOX15) and myeloperoxidase (MPO) increased, and that of the antioxidant gene (SOD2) decreased. Meanwhile, genes related to recognition and immune mediation (CD16, MYD88, TLR2), migration and cell adhesion (CX3CR1, ITGAL, ITGB2, TLN1), and the antimicrobial gene MMP9 were downregulated at 7 or 34 DFD, whereas the antimicrobial IDO1 gene was upregulated. Compared with low-producing cows, cows with high milk yield at dry-off cows had upregulated expression of the pro-inflammatory cytokines IL8 and IL18 and a greater reduction in transcript abundance of the toll-like receptor (TLR) recognition-related gene TLR2. Overall, the dry-off confirmed to be a phase of intense changes, triggering an inflammatory response and somewhat suppressing leukocyte immune function. In cows with high milk yield during the week before dry-off, the inflammatory response was exacerbated.

Pressure aimed at reducing the use of antibiotics in livestock is steadily increasing. In 2022, the prophylactic use of antibiotics for preventive purposes will be banned in the European Union (EU), including blanket therapy at dry-off. The objective of this study was to evaluate the short- and long-term effects of selectively treating cows with low somatic cell count (SCC) at dry-off using internal teat sealant with or without antibiotic therapy on udder health, milk production, metabolic, and inflammatory conditions through the next lactation. Fifteen Holstein dairy cows without intramammary infections and with SCC less than 200×103 cells/mL at dry-off were enrolled in the study. Cows were abruptly dried off and treated either with antibiotic plus teat sealant (AB) or with teat sealant only (TS). Milk and blood samples were collected on scheduled days from 10 days before dry-off to 28 days after calving. Milk composition and both inflammatory and metabolic profiles were assessed. Fertility and milk production were recorded during the previous and subsequent lactation. Rumination time was monitored from three weeks before dry-off to four weeks after calving. Data were analyzed with PROC MIXED and PROC GLM of SAS software. Total milk production, reproductive performance, rumination time, and mastitis incidence did not differ between groups. Milk yield during the first 120 days after calving was not affected by treatment. Milk composition and SCC were not affected during the first month. Compared with AB, TS had lower plasma calcium at -47 days from calving, gamma-glutamyl transferase at –50, –47, and –42, tocopherol at –65, –50, and –47, and alkaline phosphatase at 3 days from calving. Overall, both metabolic and inflammatory statuses were similar between AB and TS cows with only small transient differences. With the perspective of reducing antibiotic usage in dairy farms, internal teat sealant could be used alone in healthy cows with low SCC with no relevant effect

The dry-off of dairy cows represents an important phase of the lactation cycle, influencing the outcome of the next lactation. Among the physiological changes, the severity of the inflammatory response can vary after the dry-off, and this response might have consequences on cow adaptation in the transition period. The plasma protein profile is a diagnostic tool widely used in humans and animals to assess the inflammatory status and predict the outcome of severe diseases. The albumin-to-globulin ratio (AG) can represent a simple and useful proxy for the inflammatory condition. In this study, we investigated the relationship between AG before dry-off and inflammation, metabolic profile, and performance of 75 Holstein dairy cows. Blood samples were collected from −62 (7 d before dry-off) to 28 d relative to calving (DFC) to measure metabolic profile biomarkers, inflammatory variables, and liver function. Daily milk yield in the first month of lactation was recorded. Milk composition, body condition score, fertility, and health status were also assessed. The AG calculated 1 wk before dry-off (−62 DFC) was used to retrospectively group cows into tertiles (1.06 ± 0.09 for HI, 0.88 ± 0.04 for IN, and 0.72 ± 0.08 for LO). Data were subjected to ANOVA using the PROC MIXED program in SAS software. Differences among groups observed at −62 DFC were almost maintained throughout the period of interest, but AG peaked before calving. According to the level of acute-phase proteins (haptoglobin, ceruloplasmin, albumin, cholesterol, retinol-binding protein), bilirubin, and paraoxonase, a generally overall lower inflammatory condition was found in HI and IN than in the LO group immediately after the dry-off but also after calving. The HI cows had greater milk yield than LO cows, but no differences were observed in milk composition. The somatic cell count reflected the AG ratio trend, with higher values in LO than IN and HI either before dry-off or after calving. Fertility was better in

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis. © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Almost 25% of lung cancers (LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two parameters may improve their prognosis. Sixty-eight never-smokers LC patients with high or low CRP were selected. The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the human leukocyte antigens (HLA-DR and HLA-I), CD8, CD4, CD3, CD33, CD163, and CD68 were evaluated by immunohistochemistry on surgical samples given TIC evaluation. The classification model based on TIC scores was generated by Classification and Regression Tree analysis. Tumor mutational burden was evaluated by targeted next-generation sequencing. Exclusively high CRP (H-CRP) subset showed PD-L1 expression in 35% of LC as well as lower HLA-I and HLA-DR in their stromal cells. CD3, CD4, CD8, HLA-I, HLA-DR tumor cells staining were associated with a “low inflammatory profile” subset. CRP and LC immune profiles drive clinical outcome: 5-year survival 88% against 8% was associated with low and high-risk profiles (p < 0.0001). Clinical outcome prediction in never-smoker LC patients may be improved by both CRP and tumor immune contexture evaluation.

In visual search, salient yet task-irrelevant distractors in the stimulus array interfere with target selection. This is due to the unwanted shift of attention towards the salient stimulus-the so-called attentional capture effect, which delays deployment of attention onto the target. Although powerful and automatic, attentional capture by a salient distractor is nonetheless antagonized by distractor-filtering mechanisms and is further modulated by cross-trial contingencies: The distractor cost is typically more robust when no distraction has been experienced in the immediate past, compared to when a distractor was present on the immediately preceding trial. Here, we used transcranial magnetic stimulation (TMS) to shed light on the causal role of two crucial nodes of the ventral attention network, namely the Temporo-Parietal Junction (TPJ) and the Middle Frontal Gyrus (MFG), in the exogenous control of attention (i.e., attentional capture) and its history-dependent modulation. Participants were asked to discriminate the direction of a target arrow while ignoring a task-irrelevant salient distractor, when present. Immediately after display onset, 10 Hz triple-pulse TMS was delivered either to TPJ or MFG on the right hemisphere. Results demonstrated that stimulation of right TPJ–but not of right MFG, strongly modulated attentional capture as a function of the type of previous trial, by somewhat enhancing the distractor-related cost when the preceding trial was a distractor-absent trial and significantly decreasing the cost when the preceding trial was a distractor-present trial. These findings indicate that TMS of right TPJ exacerbates the effect of the recent history, likely reflecting enhanced updating of the predictive model that dynamically governs proactive distractor-filtering mechanisms. More generally, the results attest to a role of TPJ in mediating the history-dependent modulation of attentional capture.

Visuomotor transformations at the cortical level occur along a network where posterior parietal regions are connected to homologous premotor regions. Grasping-related activity is represented in a diffuse, ventral and dorsal system in the posterior parietal regions, but no systematic causal description of a premotor counterpart of a similar diffuse grasping representation is available. To fill this gap, we measured the kinematics of right finger movements in 17 male and female human participants during grasping of three objects of different sizes. Single-pulse transcranial magnetic stimulation was applied 100 ms after visual presentation of the object over a regular grid of 8 spots covering the left premotor cortex (PMC) and 2 Sham stimulations. Maximum finger aperture during reach was used as the feature to classify object size in different types of classifiers. Classification accuracy was taken as a measure of the efficiency of visuomotor transformations for grasping. Results showed that transcranial magnetic stimulation reduced classification accuracy compared with Sham stimulation when it was applied to 2 spots in the ventral PMC and 1 spot in the medial PMC, corresponding approximately to the ventral PMC and the dorsal portion of the supplementary motor area. Our results indicate a multifocal representation of object geometry for grasping in the PMC that matches the known multifocal parietal maps of grasping representations. Additionally, we confirm that, by applying a uniform spatial sampling procedure, transcranial magnetic stimulation can produce cortical functional maps independent of a priori spatial assumptions.SIGNIFICANCE STATEMENT Visually guided actions activate a large frontoparietal network. Here, we used a dense grid of transcranial magnetic stimulation spots covering the whole premotor cortex (PMC), to identify with accurate spatial mapping the functional specialization of the human PMC during grasping movement. Results corroborate previous finding

Animal brains contain behaviorally committed representations of the surrounding world, which integrate sensory and motor information. In primates, sensorimotor mechanisms reside in part in the premotor cortex (PM), where sensorimotor neurons are topographically clustered according to functional specialization. Detailed functional cartography of the human PM is still under investigation. We explored the topographic distribution of spatially dependent sensorimotor functions in healthy volunteers performing left or right, hand or foot, responses to visual cues presented in the left or right hemispace, thus combining independently stimulus side, effector side, and effector type. Event-related transcranial magnetic stimulation was applied to single spots of a dense grid of 10 points on the participants' left hemiscalp, covering the whole PM. Results showed: (1) spatially segregated hand and foot representations, (2) focal representations of contralateral cues and movements in the dorsal PM, and (3) distributed representations of ipsilateral cues and movements in the ventral and dorso-medial PM. The present novel causal information indicates that (1) the human PM is somatotopically organized and (2) the left PM contains sensory-motor representations of both hemispaces and of both hemibodies, but the hemispace and hemibody contralateral to the PM are mapped on a distinct, nonoverlapping cortical region compared to the ipsilateral ones.

The objective of this study was to assess how uterine disorders alter the lying behaviour and plasma biomarkers in dairy cows. 34 multiparous cows were retrospectively classified into three groups according to the first uterine disorder that cows were diagnosed with: retained placenta (RP), metritis (MET), or healthy (H; cows without any clinical disease). Lying time (LT) and duration of lying bouts (LB) were monitored between 6 weeks prior to and 8 weeks after calving via the AfiAct II pedometer. Blood samples were collected routinely between 14 days before and 28 days after calving. Data was analysed using Proc MIXED of SAS ver. 9.4. Regardless of grouping, both LT and LB were longer (P < 0.01) in the prepartum period (774 ± 16.6 min/day and 89.9 ± 2.1 min/bout) than in the first 28 days after calving (DFC; 653 ± 16.7 min/day and 63.7 ± 2.1 min/bout). Cows with RP had longer LT than healthy cows during the last 3 weeks before calving (837 ± 30.9 vs. 735 ± 27.1 min/day; P < 0.05). LT in cows with MET and healthy cows were not significantly different. The LB was similar among groups, averaging 76.1 ± 3.4 min/bout in healthy cows, 73.2 ± 3.8 min/bout in cows with RP, and 75.2 ± 3.7 min/bout in cows with MET (P > 0.05). Compared with healthy cows, cows with RP laid down longer and stood up for shorter times (P < 0.05), particularly before calving. In addition, cows with RP had increased mobilization of body stores and more pronounced inflammatory status, as demonstrated by plasma haptoglobin (P = 0.04) and albumin (P < 0.01) concentrations. Our data suggest that automatic monitoring of lying behaviour could help identify cows at increased risk of developing certain disorders, such as RP.

The transition period of dairy cattle is characterized by a number of metabolic, endocrine, physiologic, and immune adaptations, including the occurrence of negative energy balance, hypocalcemia, liver dysfunction, overt systemic inflammatory response, and oxidative stress status. The degree and length of time during which these systems remain out of balance could render cows more susceptible to disease, poor reproductive outcomes, and less efficient for milk production and quality. Studies on both monogastrics and ruminants have reported the health benefits of nutraceuticals (e.g. probiotics, prebiotics, dietary lipids, functional peptides, phytoextracts) beyond nutritional value, interacting at different levels of the animal's physiology. From a physiological standpoint, it seems unrealistic to disregard any systemic inflammatory processes. However, an alternate approach is to modulate the inflammatory process per se and to resolve the systemic response as quickly as possible. To this aim, a growing body of literature underscores the efficacy of nutraceuticals (active compounds) during the critical phase of the transition period. Supplementation of essential fatty acids throughout a 2-month period (i.e. a month before and a month after calving) successfully attenuates the inflammatory status with a quicker resolution of phenomenon. In this context, the inflammatory and immune response scenario has been recognized to be targeted by the beneficial effect of methyl donors, such as methionine and choline, directly and indirectly modulating such response with the increase of antioxidants GSH and taurine. Indirectly by the establishment of a healthy gastrointestinal tract, yeast and yeast-based products showed to modulate the immune response, mitigating negative effects associated with parturition stress and consequent disorders. The use of phytoproducts has garnered high interest because of their wide range of actions on multiple tissue targets encompassing a series of

Although affective and semantic word properties are known to independently influence our sensorimotor system, less is known about their interaction. We investigated this issue applying a data-driven mixed-effects regression approach, evaluating the impact of lexical-semantic properties on electrophysiological parameters, namely facial muscles activity (left corrugator supercilii, zygomaticus major, levator labii superioris) and heartbeat, during word processing. 500 Italian words were acoustically presented to 20 native-speakers, while electrophysiological signals were continuously recorded. Stimuli varied for affective properties, namely valence (the degree of word positivity), arousal (the amount of emotional activation brought by the word), and semantic ones, namely concreteness. Results showed that the three variables interacted in predicting both heartbeat and muscular activity. Specifically, valence influenced activation for lower levels of arousal. This pattern was further modulated by concreteness: the lower the word concreteness, the larger affective-variable impact. Taken together, our results provide evidence for bodily responses during word comprehension. Crucially, such responses were found not only for voluntary muscles, but also for the heartbeat, providing evidence to the idea of a common emotional motor system. The higher impact of affective properties for abstract words supports proposals suggesting that emotions play a central role in the grounding of abstract concepts

Although affective and semantic word properties are known to independently influence our sensorimotor system, less is known about their interaction. We investigated this issue applying a data-driven mixed-effects regression approach, evaluating the impact of lexical-semantic properties on electrophysiological parameters, namely facial muscles activity (left corrugator supercilii, zygomaticus major, levator labii superioris) and heartbeat, during word processing. 500 Italian words were acoustically presented to 20 native-speakers, while electrophysiological signals were continuously recorded. Stimuli varied for affective properties, namely valence (the degree of word positivity), arousal (the amount of emotional activation brought by the word), and semantic ones, namely concreteness. Results showed that the three variables interacted in predicting both heartbeat and muscular activity. Specifically, valence influenced activation for lower levels of arousal. This pattern was further modulated by concreteness: the lower the word concreteness, the larger affective-variable impact. Taken together, our results provide evidence for bodily responses during word comprehension. Crucially, such responses were found not only for voluntary muscles, but also for the heartbeat, providing evidence to the idea of a common emotional motor system. The higher impact of affective properties for abstract words supports proposals suggesting that emotions play a central role in the grounding of abstract concepts

In visual search, the presence of a salient, yet task-irrelevant, distractor in the stimulus array interferes with target selection and slows down performance. Neuroimaging data point to a key role of the frontoparietal dorsal attention network in dealing with visual distractors; however, the respective roles of different nodes within the network and their hemispheric specialization are still unresolved. Here, we used transcranial magnetic stimulation (TMS) to evaluate the causal role of two key regions of the dorsal attention network in resisting attentional capture by a salient singleton distractor: the frontal eye field (FEF) and the cortex within the intraparietal sulcus (IPS). The task of the participants (male/female human volunteers) was to discriminate the pointing direction of a target arrow while ignoring a task-irrelevant salient distractor. Immediately after stimulus onset, triple-pulse 10 Hz TMS was delivered either to IPS or FEF on either side of the brain. Results indicated that TMS over the right FEF significantly reduced the behavioral cost engendered by the salient distractor relative to left FEF stimulation. No such effect was obtained with stimulation of IPS on either side of brain. Interestingly, this FEF-dependent reduction in distractor interference interacted with the contingent trial history, being maximal when no distractor was present on the previous trial relative to when there was one. Our results provide direct causal evidence that the right FEF houses key mechanisms for distractor filtering, pointing to a pivotal role of the frontal cortex of the right hemisphere in limiting interference from an irrelevant but attention-grabbing stimulus.SIGNIFICANCE STATEMENT Visually conspicuous stimuli attract our attention automatically and interfere with performance by diverting resources away from the main task. Here, we applied transcranial magnetic stimulation over four frontoparietal cortex locations (frontal eye field and intraparietal sulcus

Background: Sickle cell disease (SCD) is a chronic multisystem disorder requiring comprehensive care that includes newborn screening (NBS) as the first step of care. Italy still lacks a national SCD NBS program and policy on blood disorders. Pilot single-center screening programs and a regional targeted screening have been implemented so far, but more evidence is needed in order to impact health policies. Population and methods: NBS was offered to parents of newborns in gynecology clinics in Padova and Monza, tertiary care university hospitals in northern Italy. High-performance liquid chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards. Molecular analysis of the beta-globin gene was performed on positive samples. Results: A total of 5466 newborns were enrolled; for 5439, informed consents were obtained. A similar family origin was seen in the two centers (65% Italians, 9% mixed couples, 26% immigrants). Compared with SCD NBS programs in the United States and Europe, our results show a similar incidence of SCD patients and carriers. All SCD patients had a Sub-Saharan family background; HbS carriers were 15% Caucasians (Italian, Albanians) and 10% from other areas (North Africa–India–South America); carriers of other hemoglobin variants were mainly (47%) from other areas. Conclusions: Our results demonstrate the feasibility of a multicentric NBS program for SCD, give information on HbS epidemiology in two Northern Italian Areas, and support previous European recommendation for a universal NBS program for SCD in Italy: a high incidence of patients and carriers has been detected, with a high percentage of Caucasian carriers, impossible to identify in a targeted NBS.

Patients with essential thrombocythemia (ET) often suffer from neurological symptoms (NS) not ever resulting from previous thrombotic cerebral events (TCE). We reported NS occurred in 282 patients, in order to identify the factors influencing ET-related NS in the absence of TCE, and the response to therapy. Overall, 116 of 282 patients (41%) presented NS; 101 of them (87%) reported subjective transient and fluctuating NS, without concurrent TCE, which we defined as ET-related NS, by frequency: cephalalgia, chronic paresthesias, dizziness or hypotension, visual disturbances, and tinnitus. In univariate analysis, ET-related NS resulted more frequently in young people (P = 0.017) and in females (P = 0.025). We found a higher prevalence of JAK2V617F mutation in ET-related NS patients (P = 0.021). In multivariate analysis, gender (P = 0.024) and JAK2V617F mutation (P = 0.041) remained significantly associated with the development of ET-related NS, with a risk of about four times higher for JAK2V617F-mutated patients (OR = 3.75). Ninety-seven of 101 patients with ET-related NS received an antiplatelet (AP) agent at the time of NS, whereas only selected high-risk ET-related NS patients were treated with a cytoreductive drug, according to the published guidelines and similarly to patients without NS. We observed that only 32 of 97 (33%) patients with ET-related NS achieved a complete response after AP treatment. Among the 65 non-responder patients, 36 (55.4%) improved NS after the introduction of cytoreductive therapy; therefore, the addition of cytoreductive treatment should be considered in this setting.

In the present study, we have provided clinical evidence of the predictive and prognostic relevance of tumoral PD-L1 expression and density of immune cell infiltration in BRAFV600-mutated metastatic melanoma patients treated with BRAF inhibitors

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