Effects of routine treatment with nonsteroidal anti-inflammatory drugs at calving and when lame on the future probability of lameness and culling in dairy cows: A randomized controlled trial.

Claw horn lesions (CHL) are reported as the most common cause of lameness in intensive dairy systems. Despite their prevalence, the underlying pathological mechanisms and preventive strategies for CHL remain poorly understood. Recent advances have pointed to the role of inflammation in disease aetiopathogenesis. Moderating inflammation from first calving may lead to long-term benefits and a viable intervention for treating and preventing disease. We conducted a 34-mo randomized controlled trial to investigate the effects of routine treatment with the nonsteroidal anti-inflammatory drug ketoprofen at calving and during treatment for lameness, on the future probability of lameness and culling, caused by exposure to normal farm conditions. A cohort of dairy heifers were recruited from a single, commercial dairy herd between January 8, 2018, and June 22, 2020, and randomly allocated to one of 4 treatment groups before first calving. The lactating herd was lameness scored every 2 wk on a 0 to 3 scale, to identify animals that became lame (single score ≥2a) and hence required treatment. Animals in group 1 received a therapeutic trim and a hoof block on the sound claw (if deemed necessary) every time they were treated for lameness. Animals in group 2 received the same treatment as group 1 with the addition of a 3-d course of ketoprofen (single dose daily) every time they were treated for lameness. Animals in group 3 received the same treatment as group 2 with the addition of a 3-d course of ketoprofen (single dose daily) starting 24 to 36 h after each calving. Animals in group 4 received a 3-d course of ketoprofen (single dose daily) every time they were identified with lameness. No therapeutic trim was administered to this group, unless they were identified as severely lame (a single score ≥3a). Animals were followed for the duration of the study (ending October 23, 2020). Probability of lameness was assessed by a lameness outcome score collected every 14 d. Data on culling was extracted from farm records. One hundred thirty-two animals were recruited to each group, with data from 438 animals included in the final analysis (111 in group 1, 117 in group 2, 100 in group 3, and 110 in group 4). Mixed effect logistic regression models were used to evaluate the effect of treatment group on the ongoing probability of lameness. Compared with the control group (group 1), animals in group 3 were less likely to become lame (odds ratio: 0.66) and severely lame (odds ratio: 0.28). A Cox proportional hazards survival model was used to investigate the effect of treatment group on time to culling. Compared with group 1, animals in groups 2 and 3 were at reduced risk of culling (hazard ratios: 0.55 and 0.56, respectively). The lameness effect size we identified was large and indicated that treating a cohort of animals with the group 3 protocol, would lead to an absolute reduction in population lameness prevalence of approximately 10% and severe lameness prevalence of 3%, compared with animals treated in accordance with conventional best practice (group 1).

Health care providers' awareness on medical management of children with autism spectrum disorder: cross-sectional study in Russia.

BACKGROUND: Autism spectrum disorder (ASD) is a complex developmental range of conditions that involves difficulties with social interaction and restricted/repetitive behaviors. Unfortunately, health care providers often experience difficulties in diagnosis and management of individuals with ASD, and may have no knowledge about possible ways to overcome barriers in ASD patient interactions in healthcare settings. At the same time, the provision of appropriate medical services can have positive effects on habilitative progress, functional outcome, life expectancy and quality of life for individuals with ASD. METHODS: This online survey research study evaluated the awareness and experience of students/residents (n = 247) and physicians (n = 100) in the medical management of children with ASD. It also gathered the views and experiences of caregivers to children with ASD (n = 158), all based in Russia. RESULTS: We have established that the Russian medical community has limited ASD knowledge among providers, and have suggested possible reasons for this. Based on results from online surveys completed by students/residents, non-psychiatric physicians, and caregivers of children diagnosed with ASD, the main problems pertaining to medical management of individuals with ASD were identified. Possible problem solving solutions within medical practice were proposed. CONCLUSIONS: The results from this study should be considered when implementing measures to improve healthcare practices, and when developing models for effective medical management, due to start not only in Russia but also in a number of other countries.

A history of lameness and low body condition score is associated with reduced digital cushion volume, measured by magnetic resonance imaging, in dairy cattle.

Claw horn lesions (CHL) are the result of a failing of the functional anatomy of the hoof in dairy cows. The digital cushion is understood to be a vital structure in the prevention of CHL. Claw horn lesions have previously been shown to lead to pathological change to the pedal bone; however, their effects on the digital cushion are unknown. The primary aim of this study was to examine associations between the history of CHL through an animal's life and the structure of the digital cushion at slaughter using magnetic resonance imaging. The retrospective cohort study resulted in the scanning of 102 pairs of hindfeet, collected from adult Holstein dairy cows culled from a research herd, using a 3-Tesla research-grade magnetic resonance imaging scanner. Volume and fat measurements were calculated for each digital cushion within each claw from a modified Dixon Quant sequence. Animal-level variables were constructed around the animals' lactating lifetime, with lameness scores and body condition score collected at least every 2 wk. The combined volume of digital cushion in the lateral claws was used as the outcome variable in multivariable linear models. The volume of the digital cushion was negatively associated with the number of lameness events or CHL recorded. Furthermore, animals with body condition score >3, culled later in lactation, or of a greater body weight were more likely to have a higher volume of digital cushion in the lateral claws. We propose that the observations made in the current study are the effects of a range of factors broadly associated with genetic, developmental, and disease-related inputs. Our understanding of how we can select for genetically more robust animals and how we can precondition the hoof before first calving needs to be improved to reduce the risk of future CHL in adult dairy cattle. Furthermore, understanding optimal treatment regimens and their effect on hoof anatomy may reduce the recurrence of CHL in the current lactation and future lactations.

Morphology, adipocyte size, and fatty acid analysis of dairy cattle digital cushions, and the effect of body condition score and age.

The digital cushion is an essential part of maintaining a healthy foot, working to dissipate foot strike and body weight forces and lameness from claw horn disruption lesions. Despite the importance of the digital cushion, little is known about the basic anatomy, adipocyte morphology, and fatty acid composition in relation to age, limb position, and body condition score. In total, 60 claws (from 17 cows) were selected and collected from a herd, ensuring that body condition score data and computed micro-tomography were known for each animal. Digital cushion tissue underwent histological staining combined with stereology, systematic random sampling, and cell morphology analysis, in addition to lipid extraction followed by fatty acid analysis. The results describe digital cushion architecture and adipocyte sizes. Adipocyte size was similar across all 4 claws (distal left lateral and medial and distal right lateral and medial) and across the ages (aged 2-7 yr); however, animals with body condition score of 3.00 or more at slaughter had a significantly increased cell size in comparison to those with a score of less than 2.50. Of 37 fatty acid methyl esters identified, 5 differed between either the body condition score or different age groups. C10:0 capric acid, C14:0 myristic acid, C15:0 pentadecanoic acid, and C20:0 arachidic acid percentages were all lesser in lower body condition score cows, whereas C22:1n-9 erucic acid measurements were lesser in younger cows. Saturated fatty acid, monounsaturated fatty acid, and polyunsaturated fatty acid percentages were not altered in the different claws, ages, or body condition score groups. Triglyceride quantities did not differ for claw position or age but had decreased quantities in lower body condition score animals. Digital cushion anatomy, cellular morphology, and fatty acid composition have been described in general and also in animals with differing ages, body condition scores, and in the differing claws. Understanding fat deposition, mobilization, and composition are essential in not only understanding the roles that the digital cushion plays but also in preventing disorders and maintaining cattle health and welfare.

Potential therapeutic application of mesenchymal stem cells in ophthalmology.

At present a wide variety of methods have been proposed to treat eye disorders, drug therapies are most commonly used. It should be noted that effective treatment modalities especially for degeneration of the retina and optic nerve are lacking. In the last few years stem cell transplantation has been proposed as an alternative method. The opportunities that stem cells provide within clinical use are almost unlimited. These cells are presently applied to treat various traumatic and degenerative disorders due to their unique biologic properties. Stem cells have high proliferative capabilities and are a self-maintained population of cells capable of differentiating into different cell types. Thus, they are represent a very primary stage of a cell lineage. Their ability to differentiate into different pathways provides animals with great plasticity in the renewal of somatic cells in postnatal ontogenesis. Pre-clinical and clinical ophthalmology studies where mesenchymal stem cells are applied and various methods of their administration are discussed herein. In addition the safety and efficacy of using bone marrow- and adipose tissue-derived mesenchymal stem cells have been discussed.

Peri-conception and first trimester diet modifies reproductive development in bulls.

Nutritional perturbation during gestation alters male reproductive development in rodents and sheep. In cattle both the developmental trajectory of the feto-placental unit and its response to dietary perturbations is dissimilar to that of these species. This study examined the effects of dietary protein perturbation during the peri-conception and first trimester periods upon reproductive development in bulls. Nulliparous heifers (n=360) were individually fed a high- or low-protein diet (HPeri and LPeri) from 60 days before conception. From 24 until 98 days post conception, half of each treatment group changed to the alternative post-conception high- or low-protein diet (HPost and LPost) yielding four treatment groups in a 2×2 factorial design. A subset of male fetuses (n=25) was excised at 98 days post conception and fetal testis development was assessed. Reproductive development of singleton male progeny (n=40) was assessed until slaughter at 598 days of age, when adult testicular cytology was evaluated. Low peri-conception diet delayed reproductive development: sperm quality was lowered during pubertal development with a concomitant delay in reaching puberty. These effects were subsequent to lower FSH concentrations at 330 and 438 days of age. In the fetus, the low peri-conception diet increased the proportion of seminiferous tubules and decreased blood vessel area in the testis, whereas low first trimester diet increased blood vessel number in the adult testis. We conclude that maternal dietary protein perturbation during conception and early gestation may alter male testis development and delay puberty in bulls.

Skull of the grey heron (Ardea cinerea): Detailed investigation of the orbital region.

The skull of the grey heron (Ardea cinerea) was examined with an emphasis on describing the orbital region. In the young (circa sixteen to seventeen days old) heron, the frontal bone (os frontale) and nasal bone (os nasale) comprised separate paired bones, connected by sutures (sutura interfrontalis, sutura internasalis and sutura frontonasalis plana). In adult animals, the relationship between these bones was different: the left and right frontal bone and the left and right nasal bone had grown together, and the frontal bone and nasal bone had fused into a common frontonasal bone (os frontonasale). In the ectethmoid bone (os ectethmoidale), the main components comprised of the orbital and antorbital part of the ectethmoid plate (lamina ectethmoidalis orbitalis et antorbitalis), the lateral process (processus lateralis ectethmoidalis) and the tubercle (tuberculum ectethmoidalis); the left and right ectethmoid plates were fused together to form the ectethmoid sinus (sinus ectethmoidalis) between them. In the young heron, the anatomical and functional link between the frontal and lacrimal bones did not exist yet, nor did the osseous frame of the ectethmoid-lacrimal complex. Further research into the young heron skulls is needed. This article provides novel insights into the grey heron's orbital region.

Increased dietary protein in the second trimester of gestation increases live weight gain and carcass composition in weaner calves to 6 months of age.

Genetically similar nulliparous Polled Hereford heifers from a closed pedigree herd were used to evaluate the effects of dietary protein during the first and second trimester of gestation upon foetal, placental and postnatal growth. Heifers were randomly allocated into two groups at 35 days after artificial insemination (35 days post conception (dpc)) to a single bull and fed high (15.7% CP) or low (5.9% CP) protein in the first trimester (T1). At 90 dpc, half of each nutritional treatment group changed to a high- or low-protein diet for the second trimester until 180 dpc (T2). High protein intake in the second trimester increased birth weight in females (P=0.05), but there was no effect of treatment upon birth weight when taken over both sexes. Biparietal diameter was significantly increased by high protein in the second trimester with the effect being greater in the female (P=0.02), but also significant overall (P=0.05). Placental weight was positively correlated with birth weight, fibroblast volume and relative blood vessel volume (P<0.05). Placental fibroblast density was increased and trophoblast volume decreased in the high-protein first trimester treatment group (P<0.05). There was a trend for placental weight to be increased by high protein in the second trimester (P=0.06). Calves from heifers fed the high-protein treatment in the second trimester weighed significantly more on all occasions preweaning (at 1 month (P=0.0004), 2 months (P=0.006), 3 months (P=0.002), 4 months (P=0.01), 5 months (P=0.03), 6 months (P=0.001)), and grew at a faster rate over the 6-month period. By 6 months of age, the calves from heifers fed high nutrition in the second trimester weighed 33 kg heavier than those fed the low diet in the second trimester. These results suggest that dietary protein in early pregnancy alters the development of the bovine placenta and calf growth to weaning.

Linking bone development on the caudal aspect of the distal phalanx with lameness during life.

Claw horn disruption lesions (CHDL; sole hemorrhage, sole ulcer, and white line disease) cause a large proportion of lameness in dairy cattle, yet their etiopathogenesis remains poorly understood. Untreated CHDL may be associated with damage to the internal anatomy of the foot, including to the caudal aspect of the distal phalanx upon which bone developments have been reported with age and with sole ulcers at slaughter. The primary aim of this study was to assess whether bone development was associated with poor locomotion and occurrence of CHDL during a cow's life. A retrospective cohort study imaged 282 hind claws from 72 Holstein-Friesian dairy cows culled from a research herd using X-ray micro-computed tomography (µ-CT; resolution: 0.11mm). Four measures of bone development were taken from the caudal aspect of each distal phalanx, in caudal, ventral, and dorsal directions, and combined within each claw. Cow-level variables were constructed to quantify the average bone development on all hind feet (BD-Ave) and bone development on the most severely affected claw (BD-Max). Weekly locomotion scores (1-5 scale) were available from first calving. The variables BD-Ave and BD-Max were used as outcomes in linear regression models; the explanatory variables included locomotion score during life, age, binary variables denoting lifetime occurrence of CHDL and of infectious causes of lameness, and other cow variables. Both BD-Max and BD-Ave increased with age, CHDL occurrence, and an increasing proportion of locomotion scores at which a cow was lame (score 4 or 5). The models estimated that BD-Max would be 9.8mm (SE 3.9) greater in cows that had been lame at >50% of scores within the 12mo before slaughter (compared with cows that had been assigned no lame scores during the same period), or 7.0mm (SE 2.2) greater if the cow had been treated for a CHDL during life (compared with cows that had not). Additionally, histology demonstrated that new bone development was osteoma, also termed "exostosis." Age explained much of the variation in bone development. The association between bone development and locomotion score during life is a novel finding, and bone development appears specific to CHDL. Bone development on the most severely affected foot was the best explained outcome and would seem most likely to influence locomotion score. To stop irreparable anatomical damage within the foot, early identification of CHDL and effective treatment could be critical.

Cardiomyopathy: a systematic review of disease-causing mutations in myosin heavy chain 7 and their phenotypic manifestations.

BACKGROUND: Mutations in myosin heavy chain 7 (MYH7) commonly cause cardiomyopathy. However, the relationship between mutation location, cardiomyopathy type, change in amino acid composition and disease severity is poorly understood. This systematic review aims to provide, on a large scale, important insights into the role mutations in MYH7 play in cardiomyopathy. METHODS: The literature was searched from 1966 to March 2009. The mutation location, type of mutation and disease type and severity were documented. When the severity of disease was known, the change in charge and hydropathy of the mutation was determined. Where appropriate, either a chi(2) test was used or a relative risk ratio was calculated in order to evaluate the data. RESULTS: The data presented in this study demonstrate that there are proportionately more mutations in the head and neck regions of this gene than in the tail. Importantly, mutations in the head of the gene, those that cause large changes in the hydropathy of the amino acid and non-conservative mutations are more likely to lead to a severe phenotype. CONCLUSIONS: This study suggests that mutation location in the MYH7 gene and changes in amino acid composition can have a negative impact on the disease outcome in individuals with cardiomyopathy.

Effect of gestational nutrition on vascular integrity in the murine placenta.

Maternal undernutrition is thought to result in smaller offspring and programme disease in later life. It is not known whether gestational nutrition affects development and functioning of placental vessels. The aim of this study was to ascertain if disturbed angiogenesis and junctional integrity were features of the labyrinthine vessels of placenta taken from transgenic Tie2-GFP mice fed either 18% (control) or 9% (low protein; MLP) casein diet. MLP animals showed a significant decrease in fetal weight at E14.5 and in placental and fetal weight at E18.5, however, maternal weight and litter size remained unaffected. Stereological analyses revealed that the fraction of components of the placenta remained similar in both study groups. There was a significant reduction in labyrinthine blood vessel length but not in luminal diameter in the E18.5 MLP group. In both MLP groups, perturbation of vascular endothelial Cadherin and beta-catenin, regulators of junctional integrity, permeability and quiescence, was observed with higher percentage of vessels showing weak or no junctional immunoreactivity. The reduction in length of the labyrinthine vessels and the downregulation of the adhesion molecules suggest that gestational undernutrition causes vascular dysfunction in the murine placenta. This may play a role in the early life programming of disease risk.