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We previously reported that supplementation of rumen-protected choline (RPC) reduces the hepatic triacylglycerol concentration in periparturient dairy cows during early lactation. Here, we investigated the effect of RPC on the transcript levels of lipid metabolism- related genes in liver and adipose tissue biopsies, taken at wk -3, 1, 3, and 6 after calving, to elucidate the mechanisms underlying this RPC-induced reduction of hepatic lipidosis. Sixteen multiparous cows were blocked into 8 pairs and randomly allocated to either 1 of 2 treatments, with or without RPC. Treatments were applied from 3 wk before to 6 wk after calving. Both groups received a basal diet and concentrate mixture. One group received RPC supplementation, resulting in an intake of 14.4 g of choline per day, whereas controls received an isoenergetic mixture of palm oil and additional soybean meal. Liver and adipose tissue biopsies were taken at wk -3, 1, 3, and 6 to determine the mRNA abundance of 18 key genes involved in liver and adipose tissue lipid and energy metabolism. Milk samples were collected in wk 1, 2, 3, and 6 postpartum for analysis of milk fatty acid (FA) composition. The RPC-induced reduction in hepatic lipidosis could not be attributed to altered lipolysis in adipose tissue, as no treatment effect was observed on the expression of peroxisome proliferator-activated receptor γ, lipoprotein lipase, or FA synthase in adipose tissue, or on the milk FA composition. Rumen-protected choline supplementation increased the expression of FA transport protein 5 and carnitine transporter SLC22A5 in the liver, suggesting an increase in the capacity of FA uptake and intracellular transport, but no treatment effect was observed on carnitine palmitoyl transferase 1A, transporting long-chain FA into mitochondria. In the same organ, RPC appeared to promote apolipoprotein B-containing lipoprotein assembly, as shown by elevated microsomal triglyceride transfer protein expression and apolipoprotein B100 expression. Cows supplemented with RPC displayed elevated levels of glucose transporter 2 mRNA and a reduced peak in pyruvate carboxylase mRNA immediately after calving, showing that supplementation also resulted in improved carbohydrate metabolism. The results from this study suggest that RPC supplementation reduces liver triacylglycerol by improved FA processing and very-low-density lipoprotein synthesis, and RPC also benefits hepatic carbohydrate metabolism. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between oxidative damage and the effect of vitamin E supplementation in blood, milk, and liver tissue in 16 periparturient heifers. The question is whether measurements of oxidative and vitamin E status in blood of a periparturient cow are representative of the total body, given that blood concentrations of both vitamin E and oxidative stress products change around this period. The daily vitamin E intake of the vitamin E-supplemented Holstein -Friesian heifers (n = 8) was 3,000 international units and was started 2 mo before calving; the control heifers (n = 8) were not supplemented. Oxidative damage was determined on the basis of malondialdehyde (MDA) concentrations. Blood was sampled 9 times before calving, on calving day, and twice after calving. Liver biopsies were taken at wk -5, -1, and 2 relative to calving day. Milk was obtained from all heifers immediately after calving, the first 2 milkings and on d 3, 7, and 14 at 0600 h. Serum and liver tissue were analyzed for vitamin E, cholesterol, and MDA; and milk samples were analyzed for vitamin E, MDA, fat, protein, and somatic cell count. The results showed that vitamin E supplements increased both absolute vitamin E concentrations and the ratio of vitamin E to cholesterol in blood and liver tissue. Absolute vitamin E concentration in milk tended to be greater in supplemented cows. Based on the increased MDA blood concentrations at calving, it seems that dairy heifers experience oxidative stress. The effect of vitamin E on MDA differs between the blood, liver, and mammary gland. Vitamin E supplementation could not prevent the increase in blood MDA at calving, but the significantly lower MDA blood concentrations of supplemented cows in the 2 wk after calving suggest that vitamin E has a role in recovery from parturition-related oxidative stress. Vitamin E supplementation reduced oxidative damage in liver, whereas no obvious effect was found on milk MDA concentrations. A strong relationship was found between blood and liver vitamin E and the ratio of vitamin E to cholesterol. Concentrations of MDA in blood and milk were also strongly related. The results show that the relationship between oxidative damage and vitamin E differs within blood, liver tissue, and milk. This implies that oxidative and vitamin E status calculated on the basis of blood values alone should be interpreted with caution and cannot be extrapolated to the whole animal. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral dystrophy (FSHD) is an inherited muscle disorder that manifests in childhood in 20% of patients. Understanding the natural history of childhood FSHD and establishing appropriate clinical and functional outcome measures is crucial to successfully prepare for clinical trials and benefits patient care and education. We examined the disease's course in children over a 5-year follow-up, identifying outcome measures sensitive to change at different time points in a population still undergoing normal growth. In a prospective nationwide cohort of 20 type 1 FSHD patients with childhood-onset, assessments of impairments and physical disability after 5 years of follow-up were added to the earlier measurements at baseline and 2 years. The assessments included manual muscle testing, functional muscle tests, FSHD clinical score (FSHD-CS), FSHD clinical severity scale (FSHD-CSS), and muscle imaging using standardized muscle ultrasonography (MUS). Furthermore, patient-reported questionnaires on pain, fatigue, and quality of life (QoL) were completed. 18/20 patients (aged 2 to 17 years at baseline) completed the follow-up. None of the participants lost ambulation or required assisted ventilation. Disease progression was variable; the mean increase in FSHD-CS was 1.6 points (range -1 to 4). Despite objective disease progression, most participants (89%) did not perceive change. Extra-muscular complications were rare. Half of the children reported pain, mostly located in the shoulder region. The NeuroQoL fatigue demonstrated a decrease in fatigue levels, quality of life as measured by the Kidscreen-52 improved in all domains during follow-up (mean z-score at baseline -0.9 and 0.2 during the 5-year follow-up, p=0.01). Most sensitive outcome measures for detecting progression were the FSHD-CS (SRM 1.07) and FSHD-CSS (SRM: 0.92), followed by MUS (SRM: 0.68). The progression rate could not be predicted from baseline. We observed variable disease progression over 5 years, which remained unnoticed by most participants. Compared to earlier findings in other populations, this cohort presents a milder early-onset phenotype. This is likely related to the current practice of genetic testing at an early stage in mildly affected children from FSHD-affected families in Netherlands. This development may prompt a reevaluation of the classification of early-onset FSHD. Compared to the 2-year follow-up, this study showed improvement of QoL and lower fatigue levels, possibly caused by improved coping mechanism of patients with a longer disease duration. The FSHD-CS, FSHD-CSS and MUS were most sensitive detecting disease progression after 5 years, but the responsiveness to change of the different endpoints varies across the distinct time points. The relatively slow progression combined with physiological growth emphasizes the need to identify endpoints sensitive to change within 1-2 years before the start of trials. We suggest including MUS and FSHD-COM into future studies, evaluating the reachable workspace in the pediatric population, and exploring the feasibility of creating a larger cohort through international collaboration. [ABSTRACT FROM AUTHOR]

The effects of a dietary supplement of rumen-protected choline on feed intake, milk yield, milk composition, blood metabolites, and hepatic triacylglycerol were evaluated in periparturient dairy cows. Thirty-eight multiparous cows were blocked into 19 pairs and then randomly allocated to either one of 2 treatments. The treatments were supplementation either with or without (control) rumen-protected choline. Treatments were applied from 3 wk before until 6 wk after calving. Both groups received the same basal diet, being a mixed feed of grass silage, corn silage, straw, and soybean meal, and a concentrate mixture delivered through transponder-controlled feed dispensers. For all cows, the concentrate mixture was gradually increased from 0 kg/day (wk -3) to 0.9 kg of dry matter (DM)/d (day of calving) and up to 8.1 kg of DM/d on d 17 postcalving until the end of the experiment. Additionally, a mixture of 60 g of a rumen-protected choline supplement (providing 14.4 g of choline) and of 540 g of soybean meal or a (isoenergetic) mixture of 18 g of palm oil and 582 g of soybean meal (control) was offered individually in feed dispensers. Individual feed intake, milk yield, and body weight were recorded daily. Milk samples were analyzed weekly for fat, protein, and lactose content. Blood was sampled at wk -3, d 1, d 4, d 7, d 10, wk 2, wk 3, and wk 6 and analyzed for glucose, nonesterified fatty acids, and β-hydroxybutyric acid. Liver biopsies were taken from 8 randomly selected pairs of cows at wk -3, wk 1, wk 4, and wk 6 and analyzed for triacylglycerol concentration. We found that choline supplementation increased DM intake from 14.4 to 16.0 kg/d and, hence, net energy intake from 98.2 to 109.1 MJ/d at the intercept of the lactation curve at 1 day in milk (DIM), but the effect of choline on milk protein yield gradually decreased during the course of the study. Choline supplementation had no effect on milk yield, milk fat yield, or lactose yield. Milk protein yield was increased from 1.13 to 1.26 kg/d at the intercept of the lactation curve at 1 DIM, but the effect of choline on milk protein yield gradually decreased during the course of the study. Choline supplementation was associated with decreased milk fat concentration at the intercept of the lactation curve at 1 DIM, but the effect of choline on milk fat concentration gradually decreased as lactation progressed. Choline supplementation had no effect on energy-corrected milk yield, energy balance, body weight, body condition score, and measured blood parameters. Choline supplementation decreased the concentration of liver triacylglycerol during the first 4 wk after parturition. Results from this study suggest that hepatic fat export in periparturient dairy cows is improved by choline supplementation during the transition period and this may potentially decrease the risk for metabolic disorders in the periparturient dairy cow. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of vitamin E supplementation on oxidative status in blood, liver, milk, and ovarian follicular fluid in periparturient heifers. Vitamin E supplementation started 8 wk before calving and continued until 8 wk postpartum. Grass silage was the main forage fed during the experiment. In addition, supplemented heifers (n=9) received 3,000IU of vitamin E daily on a carrier food; control heifers (n=9) consumed only the carrier food. Blood samples and liver biopsies were taken frequently throughout the study and ovarian follicular fluid was sampled at 8 wk postpartum. Body condition score was scored weekly and milk yield was measured daily. A marker of oxidative damage, determinable reactive oxygen metabolites (d-ROM), and a set of antioxidants were measured in blood, liver, milk, and ovarian follicular fluid. Control heifers had a low vitamin E status, and selenium status was marginal in control and supplemented heifers. Vitamin E supplementation increased vitamin E concentrations in blood, liver, and ovarian follicular fluid and increased triacylglycerol in liver. Serum d-ROM were not reduced by vitamin E supplementation. Superoxide dismutase and glutathione peroxidase activity in red blood cells and liver and glutathione peroxidase activity in ovarian follicular fluid were not affected by vitamin E supplementation and they were not increased around calving. Protein thiol groups and ratio of reduced glutathione to oxidized glutathione were also not increased around calving. These results suggest that heifers around calving experience a low level of oxidative processes. This might be caused by lower than expected milk production attributed to a low forage intake. Serum d-ROM were negatively correlated with protein thiol groups and positively correlated with the activity of glutathione peroxidase in red blood cells, oxidized glutathione, and the ratio of reduced glutathione and oxidized glutathione in serum. The lack of treatment effects allowed estimation of the effects of body condition 4 wk before calving and the loss of body condition on markers of lipid peroxidation and antioxidants. A trend that a body condition of ⩾3 might result in more oxidative damage measured by serum d-ROM was observed, but fatter heifers had a significantly higher ratio of reduced glutathione to oxidized glutathione. [ABSTRACT FROM AUTHOR]

A correction to the article "Effect of rumen-protected choline on performance, blood metabolites, and hepatic triacylglycerols of periparturient dairy cattle," that was published in a 2011 issue is presented.

Extending the voluntary waiting period (VWP) for insemination in dairy cows is of interest as a strategy to reduce the frequency of calving events and inseminate at a moment with fewer fertility problems. Little is known about the calves born from dams with a different VWP followed by a different calving interval (CInt). The objective of the current study was to identify the effect of dam's CInt on body condition, metabolic status, and milk production of their offspring from birth until 100 DIM of the offspring's first lactation. Holstein-Friesian dairy cows (n = 154, 41 primiparous, 113 multiparous) were blocked according to parity, milk yield, and SCC and randomly assigned to a VWP of 50, 125, or 200 d. Female calves (n = 62) from cows with different CInt were monitored from birth until their first calving event as heifer. Certain dams were not successfully inseminated soon after the planned VWP, resulting in differences between the intended VWP and the actual CInt. Calves were regrouped according to their dam's actual CInt (CInt_1: 324-408 d; CInt_2: 409-468 d; CInt_3: 469-586 d). The dam's CInt did not affect calf birth weight. From birth to weaning, the calves born to dams in CInt_1 had a higher plasma nonesterified fatty acids (NEFA) concentration (0.34 mmol/L; CI: 0.30, 0.37) than CInt_2 (0.28 mmol/L; CI: 0.26, 0.31) and CInt_3 (0.26 mmol/L; CI: 0.24, 0.29) calves. Calves born to dams with a shorter CInt (CInt_1) had greater IgG and IgM against keyhole limpet hemocyanin (KLH) than CInt_3 (IgG: 6.05 ± 0.30 vs. 4.64 ± 0.30; IgM: 6.45 ± 0.17 vs. 5.89 ± 0.16, respectively; mean ± SE) before weaning. After weaning till calving, CInt_1 calves tended to have greater plasma NEFA concentration than CInt_3-calves. During the first 100 DIM, a longer CInt of the dams resulted in lower plasma IGF_1 (CInt_2), lower milk lactose (CInt_3), and lower fat- and protein-corrected milk (FPCM; CInt_2) in offspring, compared with shorter CInt of the dams (CInt_1). Collectively, a longer CInt in dams did not affect birth weight of their calves or BW during the weaning or rearing phase. From birth till weaning, a longer CInt in dams resulted in less anti-KLH IgG and lower plasma NEFA concentration in plasma of the calves. During the first lactation of their offspring, a longer CInt in dams can result in a lower plasma IGF_1 and FPCM during the first 100 DIM, although effects were not present in all CInt categories., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The early lactation period in dairy cows is characterized by complex interactions among energy balance (EB), disease, and alterations in metabolic and inflammatory status. The objective of this study was to cluster cows based on EB time profiles in early lactation and investigate the association between EB clusters and inflammatory status, metabolic status, oxidative stress, and disease. Holstein-Friesian dairy cows (n = 153) were selected and monitored for disease treatments during wk 1 to 6 in lactation. Weekly EB was calculated based on energy intake and energy requirements for maintenance and milk yield in wk 1 to 6 in lactation. Weekly plasma samples were analyzed for metabolic variables in wk 1 to 6, and inflammatory and oxidative stress variables in wk 1, 2, and 4 in lactation. Liver activity index (LAI) was computed from plasma albumin, cholesterol, and retino-binding protein concentration. First, cows were clustered based on time profiles of EB, resulting in 4 clusters (SP: stable positive; MN: mild negative; IN: intermediate negative; SN: severe negative). Cows in the SN cluster had higher plasma nonesterified fatty acids and BHB concentrations, compared with cows in the SP cluster, with the MN and IN clusters being intermediate. Cows in the SN cluster had a higher milk yield, lower DMI in wk 1, lower insulin concentration compared with cows in the SP cluster, and lower glucose and IGF-1 concentration compared with cows in the SP and MN clusters. Energy balance clusters were not related to plasma haptoglobin, cholesterol, albumin, paraoxonase, and LAI. Second, cows were grouped based on health status: IHP, cows with treatment for inflammatory health problem (endometritis, fever, clinical mastitis, vaginal discharge or retained placenta); OHP, cows with no IHP but treatment for other health problem (milk fever, cystic ovaries, claw and leg problems, rumen and intestine problems, or other diseases); and NHP, cows with no treatments, in the first 6 wk after calving. Energy balance was not different among health status groups. The IHP cows had lower nonesterified fatty acids and greater insulin concentration in plasma compared with OHP cows. The IHP cows had lower plasma albumin concentration, lower LAI, and higher haptoglobin concentration compared with OHP and NHP. Overall, EB time profiles were associated with the metabolic status of dairy cows in early lactation, but were only limitedly related to markers of inflammation and oxidative stress status. Inflammatory and metabolic status were related to disease events in early lactation and caused prolonged effects on liver metabolism., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Omitting or shortening the dry period may result in a fairly constant ration throughout the transition period of dairy cows, reducing the need for adaptation of cow metabolism and rumen function to a new lactation. The objective of this study was to determine the effect of dry period length (DP) on rumen adaptation and cow metabolic state during the transition period. Twelve pregnant, rumen-cannulated Holstein Friesian dairy cows at the end of their first lactation were assigned to 1 of 3 treatments: a conventional (60 d), short (30 d), or no dry period (0 d). At dry-off, cows received a dry-cow ration until calving. Lactating cows received a lactation ration. Cows were monitored from 8 wk before calving until 8 wk after calving for milk yield and DMI. Rumen biopsies were taken from 3 locations in the rumen at 60, 40, and 10 d before calving and 3, 7, 14, 28, and 56 d after calving to assess papillae dimensions. Blood was sampled weekly from 3 wk before until 8 wk after calving, and liver biopsies were taken at wk -2, 2, and 4 relative to calving. Prepartum, DMI, and milk yield were greater for cows with a short or no dry period, compared with cows with a conventional dry period. Postpartum, DMI was greater for cows with a short dry period compared with cows with a conventional dry period. Plasma glucose concentration was greater for cows without a dry period, compared with the other DP postpartum. Plasma concentrations of nonesterified fatty acids and BHB, and liver triglyceride content, did not differ among dry period. Rumen papillae differed in size based on biopsy location, but there was no interaction between biopsy location and the effect of DP. Rumen papillae surface area for cows managed for a 30- or 60-d dry period decreased toward calving. At 40 d prepartum, papillae surface area was greater for short and no dry period treatment compared with a conventional dry period. At 10 d prepartum, papillae surface area was greater for the no dry period treatment compared with both other treatments, and this difference was still present 3 d postpartum. Cows managed for a short dry period showed faster increase in papillae dimensions after calving compared with cows managed for a conventional dry period. From d 28 onwards, no differences in papillae surface area were observed. The faster rumen adaptation postpartum may be related to the increased DMI during the first weeks postpartum for cows managed for a short dry period. However, this did not result in improved metabolic status or milk yield. The results from the present study demonstrate that the dietary changes related to a conventional DP affected rumen papillae development, not only prepartum but also early postpartum. Further optimization of DP as well as dietary composition throughout the transition period may support cows in their adaptation to a new lactation., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Based on modeling studies, a 1-yr calving interval for dairy cows is generally considered optimal from an economic point of view. Recently some dairy farmers are deliberately extending the voluntary waiting period for insemination (VWP) to extend the calving interval. Reasons to extend the VWP are to reduce the frequency of transitions such as dry-off and calving to improve health, to reduce labor associated with these transitions, and to reduce the number of surplus calves. This study aimed to evaluate yearly revenues, yearly costs, and yearly net partial cash flow (NPCF) for individual cows with a VWP of 50, 125, or 200 d based on data from a randomized control trial. The NPCF included revenues and costs for milk yield, calves born, inseminations, concentrate supply, partial mixed ration (PMR) supply, veterinary treatments, discarded milk due to veterinary treatments, culling, and labor (for milking, calving cows, inseminations, and veterinary treatments). Holstein-Friesian dairy cows (n = 153) within one herd were blocked for parity, calving season, and expected (primiparous cows) or previous (multiparous cows) 305-d milk yield. Cows were randomly assigned within the blocks to 1 of 3 VWP (VWP50, VWP125, or VWP200) in wk 6 after calving, and monitored from wk 6 after calving until wk 6 after the next calving or until culling. Revenues and costs were calculated per individual cow and expressed per cow per year. Revenues from milk and costs for PMR and concentrate contributed most to the yearly NPCF. Total yearly revenues were greater in VWP50 compared with VWP200 (€3,169 vs. €2,832), mainly because of €334 greater milk revenues. Total yearly costs were also greater in VWP50 compared with VWP200 (€1,964 vs. €1,729), mainly because of €102 greater concentrate costs. The VWP was not significantly associated with the NPCF per cow per year. A change in milk, feed, or calf price, or a change in labor costs for calving cows or for inseminations had a greater effect on the yearly NPCF of cows in VWP50 compared with cows in VWP200. To investigate variation in NPCF, cows were grouped for yearly NPCF and categorized into 3 economic classes (EC): EC1 (<€1,100/yr), EC2 (€1,100-€1,400/yr), and EC3 (>€1,400/yr). Cows in EC3 had greatest lactation production per day in the experiment (i.e., kg of milk, protein, fat, lactose), and lowest number of veterinary treatments during the experiment., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The form of oral calcium (Ca) supplement and the Ca source influence Ca absorption dynamics resulting in different postpartum calcemia. The objective of this study was to investigate whether an oral Ca supplement (mainly CaCO3) offered for voluntary consumption would maintain or increase postpartum blood Ca to the same degree as a Ca bolus (mainly CaCl2) providing an equivalent dose of a Ca. A total of 72 Holstein cows were blocked by expected parturition date and parity. Within each block of 3 animals, cows were randomly assigned to one of three treatments, including an oral Ca supplement offered for voluntary consumption (Ca-drink, n = 23), an oral Ca bolus (Ca-bolus, n = 24), or an untreated group (CON, n = 25). Treatments were administered once within 15 min postpartum. The Ca-drink provided 45 g of Ca (CaCO3 source) and was mixed in 20 L of lukewarm water and offered to cows for 30 min. The Ca-bolus provided 43 g of Ca (71% from CaCl2 and 29% from CaSO4) and was administered once. Both Ca-bolus and CON cows received 20-l of lukewarm water at parturition to standardize the volume of fluids (Ca-drink or 20-l lukewarm water) offered at parturition. Dairy cows offered Ca-drink had a 28% higher fluid consumption than Ca-bolus and CON cows. Milk yield and milk composition expressed in percentage protein, fat, lactose, and urea did not differ, whilst there was a small but significant increase in DMI in cows receiving the Ca-drink compared to CON, while Ca-bolus did not differ from other groups. This was consistent with reduced BW losses between week 1 and 3 in cows receiving the Ca-drink suspension. Treatment by time interactions were present for blood Ca, glucose, and urea concentrations. Blood Ca was relatively stable in Ca-drink cows, while higher fluctuations were observed in Ca-bolus cows. In Ca-bolus cows, blood Ca increased from 15 min to 6 h, decreased from 6 to 24 h, and finally increased again from 24 to 48 h. At 24 h post administration, blood Ca was greater in cows receiving the Ca-drink than cows receiving the Ca-bolus. Blood glucose was greater in Ca-bolus cows at 15 min after treatment administration compared with Ca-bolus and CON, while blood urea was higher in CON than Ca-drink and Ca-bolus throughout the sampling period. These results indicate that voluntary oral Ca resulted in a relatively stable calcemia, whereas higher fluctuations were observed in cows receiving the Ca-bolus. Due to a lack of differences between Ca-drink and Ca-bolus compared with CON, it is not possible to conclude regarding the efficacy in maintaining postpartum blood Ca.

Background: Facioscapulohumeral dystrophy (FSHD) is an inherited muscular dystrophy clinically characterised by muscle weakness starting with the facial and upper extremity muscles. A disease model has been developed that postulates that failure in somatic repression of the transcription factor DUX4 embedded in the D4Z4 repeat on chromosome 4q causes FSHD. However, due to the position of the D4Z4 repeat close to the telomere and the complex genetic and epigenetic aetiology of FSHD, there is ongoing debate about the transcriptional deregulation of closely linked genes and their involvement in FSHD., Method: Detailed genetic characterisation and gene expression analysis of patients with clinically confirmed FSHD and control individuals., Results: Identification of two FSHD families in which the disease is caused by repeat contraction and DUX4 expression from chromosome 10 due to a de novo D4Z4 repeat exchange between chromosomes 4 and 10. We show that the genetic lesion causal to FSHD in these families is physically separated from other candidate genes on chromosome 4. We demonstrate that muscle cell cultures from affected family members exhibit the characteristic molecular features of FSHD, including DUX4 and DUX4 target gene expression, without showing evidence for transcriptional deregulation of other chromosome 4-specific candidate genes., Conclusion: This study shows that in rare situations, FSHD can occur on chromosome 10 due to an interchromosomal rearrangement with the FSHD locus on chromosome 4q. These findings provide further evidence that DUX4 derepression is the dominant disease pathway for FSHD. Hence, therapeutic strategies should focus on DUX4 as the primary target., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Our aim was to evaluate the effects of a low or high dietary phosphorus (P) concentration during the dry period, followed by either a high or low dietary P concentration during the first 8 wk of lactation, on plasma Ca concentrations, feed intake, and lactational performance of dairy cattle. Sixty pregnant multiparous Holstein Friesian dairy cows were assigned to a randomized block design with repeated measurements and dietary treatments arranged in a 2 × 2 factorial fashion. The experimental diets contained 3.6 (Dry-HP) or 2.2 (Dry-LP) g of P/kg of dry matter (DM) during the dry period, and 3.8 (Lac-HP) or 2.9 (Lac-LP) g of P/kg of DM during 56 d after calving period. In dry cows, plasma Ca concentrations were 3.3% greater when cows were fed 2.2 instead of 3.6 g of P/kg of DM. The proportion of cows being hypocalcemic (plasma Ca concentrations <2 mM) in the first week after calving was lowest with the low-P diets both during the dry period and lactation. Plasma Ca concentrations in wk 1 to 8 after calving were affected by dietary P level in the dry period and in the lactation period, but no interaction between both was present. Feeding Dry-LP instead of Dry-HP diets resulted in 4.1% greater plasma Ca values, and feeding Lac-LP instead of Lac-HP diets resulted in 4.0% greater plasma Ca values. After calving, plasma inorganic phosphate (Pi) concentrations were affected by a 3-way interaction between sampling day after calving, and dietary P levels during the dry period and lactation. From d 1 to d 7 postpartum, cows fed Lac-HP had increased plasma Pi concentrations, and the rate appeared to be greater in cows fed Dry-LP versus Dry-HP. In contrast, plasma Pi concentrations decreased from d 1 to d 7 postpartum in cows fed Lac-LP, and this decrease was at a higher rate for cows fed Dry-HP versus Dry-LP. After d 7, plasma Pi concentrations remained rather constant at 1.5 to 1.6 mM when cows received Lac-HP, whereas with Lac-LP plasma Pi concentrations reached stable levels (i.e., 1.3-1.4 mM) at d 28 after calving. Milk production, DM intake, and milk concentrations of P, Ca, fat, protein, and lactose were not affected by any interaction nor the levels of dietary P. It is concluded that the feeding of diets containing 2.2 g of P/kg of DM during the last 6 wk of the dry period and 2.9 g of P/kg of DM during early lactation increased plasma Ca levels when compared with greater dietary P levels. These low-P diets may be instrumental in preventing hypocalcemia in periparturient cows and do not compromise DM intake and milk production. Current results suggest that P requirements in dairy cows during dry period and early lactation can be fine-tuned toward lower values than recommended by both the National Research Council and the Dutch Central Bureau for Livestock Feeding. Caution however is warranted to extrapolate current findings to entire lactations because long-term effects of feeding low-P diets containing 2.9 of g/kg of DM on production and health needs further investigation., (Copyright © 2021 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

A 1-yr calving interval (CInt) is usually associated with maximized milk output, due to the calving-related peak in milk yield. Extending CInt could benefit cow health and production efficiency due to fewer transition periods per unit of time. Extending CInt can affect lactation performance by fewer days dry per year, delayed pregnancy effect on milk yield, and greater milk solid yield in late lactation. This study first investigated the effects of 3 different voluntary waiting periods (VWP) from calving until first insemination on body weight, body condition, milk yield, and lactation persistency. Second, individual cow characteristics in early lactation were identified that contributed to milk yield and persistency of cows with different VWP. Holstein-Friesian dairy cows (n = 154) within 1 herd were blocked for parity, calving season, and expected milk yield. Cows were randomly assigned within the blocks to 1 of 3 VWP (50, 125, or 200 d: VWP50, VWP125, or VWP200, respectively) and monitored through 1 complete lactation and the first 6 wk of the subsequent lactation, or until culling. Minimum and mean CInt (384 vs. 452 vs. 501 d for VWP50 vs. VWP125 vs. VWP200) increased with increasing VWP, but maximum CInt was equal for the 3 VWP. Fat- and protein-corrected milk yield (FPCM) was analyzed weekly. Milk yield and FPCM were also expressed per day of CInt, to compare yields of cows with different VWP. Persistency was determined between d 100 and d 200 of the lactation, as well as between d 100 and dry-off. Values are presented as least squares means ± standard error of the mean. During the first 44 wk of lactation, VWP did not affect FPCM yield in both primiparous and multiparous cows. The VWP did not affect milk yield per day of CInt. The VWP did not affect FPCM yield per day of calving interval for primiparous cows. Multiparous cows in VWP125 had FPCM yield per day of CInt similar to that of VWP50. Multiparous cows in VWP200 had lower FPCM yield per day of CInt compared with VWP50 (27.2 vs. 30.4 kg/d). During the last 6 wk before dry-off, cows in VWP125 had lower yield compared with cows in VWP50, which could benefit their udder health in the dry period and after calving. Persistency was better for cows in VWP200 compared with cows in VWP50 (-0.05 vs. -0.07 kg/d). Body weight was not different among VWP groups. Multiparous cows in VWP200 had a higher body condition score in the last 3 mo before dry-off and the first 6 wk of the next lactation, compared with multiparous cows in VWP125 and VWP50. The VWP could be extended from 50 d to 125 d without an effect on daily yield per day of calving interval. Extending VWP until 200 d for primiparous cows did not affect their daily milk yield, but multiparous cows with a 200-d VWP had a reduced milk yield per day of calving interval and an increased body condition in late lactation and the subsequent lactation, compared with multiparous cows with a 50-d VWP., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Drying-off, calving, and start of lactation are critical transition events for a dairy cow. As a consequence, most animal health issues occur during these periods. By extending the voluntary waiting period for first insemination after calving, calving interval (CInt) can be extended, with possible positive effects for fertility and health. Some cows might be better suited for an extended CInt than others, due to differences in milk yield level, lactation persistency, or health status, which would justify a customized CInt based on individual cow characteristics. This study aims to investigate 13 farms with customized CInt, with respect to calving to first service interval (CFSI), accomplished CInt, services per conception (SC), conception rate at first artificial insemination (CR1AI), peak yield, lactation persistency, 305-d yield, and effective lactation yield. In total, 4,858 complete lactations of Holstein Friesian cows between 2014 and 2019 from the 13 farms were grouped by parity (1 or 2+) and CFSI (CFSI class; CFSI-1 < 84; 84 ≤ CFSI-2 < 140; 140 ≤ CFSI-3 < 196; 196 ≤ CFSI-4 < 252, CFSI-5 ≥ 252 d) or CInt (CInt class; CInt-1 < 364; 364 ≤ CInt-2 < 420; 420 ≤ CInt-3 < 476; 476 ≤ CInt-4 < 532, CInt-5 ≥ 532 d). Cow inseminations, available for 11 out of 13 farms (3,597 complete lactations), were grouped by parity (1 and 2+) and CFSI class or CInt class. The fertility and milk production characteristics were analyzed with generalized and general linear mixed models. The CFSI class was not associated with SC, but extended CInt class was associated with increased SC (CInt-1-5; 1.11-3.70 SC). More than 50% of cows in the CFSI class <84 d ended up in longer than expected CInt (>364 d), showing that these cows were not able to conceive for the desired CInt. More than 50% of cows in CInt classes 3 and higher (CInt ≥ 420 d) had an earlier first insemination before successful insemination (CFSI class 1; <196 d), showing that these extended CInt classes consisted of both cows with an extended waiting period for first insemination and cows that failed to conceive at earlier insemination(s). On most farms, lactation persistency was greatest in CInt class 1 (<364 d), probably related to the low peak yield in this class. When this shortest CInt class was excluded, persistency increased with extended CInt classes on most farms. Although at the majority of farms 305-d yield was greater in CInt ≥ 532 d, effective lactation yield at most farms was greatest in CInt from 364 to 531 d, especially for multiparous cows. Based on the results of this study, a CInt between 364 and 531 days seems most optimal for milk production, when high-yielding cows were selected., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

A need exists for biomarkers to diagnose, quantify and longitudinally follow facioscapulohumeral muscular dystrophy (FSHD) and many other neuromuscular disorders. Furthermore, the pathophysiological mechanisms leading to muscle weakness in most neuromuscular disorders are not completely understood. Dynamic ultrasound imaging (B-mode image sequences) in combination with speckle tracking is an easy, applicable and patient-friendly imaging tool to visualize and quantify muscle deformation. This dynamic information provides insight in the pathophysiological mechanisms and may help to distinguish the various stages of diseased muscle in FSHD. In this proof-of-principle study, we applied a speckle tracking technique to 2-D ultrasound image sequences to quantify the deformation of the tibialis anterior muscle in patients with FSHD and in healthy controls. The resulting deformation patterns were compared with muscle ultrasound echo intensity analysis (a measure of fat infiltration and dystrophy) and clinical outcome measures. Of the four FSHD patients, two patients had severe peroneal weakness and two patients had mild peroneal weakness on clinical examination. We found a markedly varied muscle deformation pattern between these groups: patients with severe peroneal weakness showed a different motion pattern of the tibialis anterior, with overall less displacement of the central tendon region, while healthy patients showed a non-uniform displacement pattern, with the central aponeurosis showing the largest displacement. Hence, dynamic muscle ultrasound of the tibialis anterior muscle in patients with FSHD revealed a distinctively different tissue deformation pattern among persons with and without tibialis anterior weakness. These findings could clarify the understanding of the pathophysiology of muscle weakness in FSHD patients. In addition, the change in muscle deformation shows good correlation with clinical measures and quantitative muscle ultrasound measurements. In conclusion, dynamic ultrasound in combination with speckle tracking allows the study of the effects of muscle pathology in relation to strength, force transmission and movement generation. Although further research is required, this technique can develop into a biomarker to quantify muscle disease severity., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Postural instability is a disabling feature of Parkinson's disease (PD), contributing to recurrent falls and fall-related injuries. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, and is therefore a key component of the neurological examination in PD. Many variants exist, which confuses both clinical practice and research. Here, we evaluate the merits of this test by discussing three common variants: (1) the pull test as described in the MDS-UPDRS scale; (2) using an unexpected shoulder pull, without prior warning; and (3) the push-and-release test. All variants are a quick method to index the degree of postural instability, but the outcome can vary considerably due to variability in test execution and -interpretation. This partially explains why the retropulsion test fails to predict future falls in PD. Another explanation is that falling results from the complex interplay between gait, balance, cognitive decline and environmental factors, and the retropulsion test captures only part of that. We conclude with several recommendations for current clinical practice.

The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD) between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation.