Key determinants of adaptive strategies of goats to a 2-day nutritional challenge during early lactation.

Little is known about the key determinants of the physiological adaptations to environmental challenges and how these determinants interact. We evaluated how the response/recovery profiles to a short-term nutritional challenge during early lactation are affected by early-life nutritional strategies in dairy goats divergently selected for functional longevity. We used 72 females, split into two cohorts, daughters of Alpine bucks divergently selected for functional longevity. The females from the two lines were fed with two divergent diets, normal vs low-energy, from weaning until the middle of first gestation, and then fed with the same standard diet. Individual BW, body condition score, morphology, and plasma samples were collected from birth to first kidding. The adaptative physiological strategy to a nutritional challenge was assessed via a 2-day feed restriction challenge, during early lactation, which consisted of a five-day control period on a standard lactation diet followed by a 2-day challenge with straw-only feeding and then a 10-day recovery period on a standard lactation diet. During the challenge, DM intake, BW, milk yield (MY), and plasma and milk metabolite composition were recorded daily. Linear mixed-effects models were used to analyze all traits, considering the individual nested in the cohort as a random effect and the 2 × 2 treatments (i.e., line and rearing diet) and litter size as fixed effects. Linear mixed-effects models using a piecewise arrangement were used to analyze the response/recovery profiles to nutritional challenge. Random parameters estimated for each individual, using the mixed-effects models without the fixed effects of rearing diet and genetic line, were used in a stepwise model selection based on R2 to identify key determinants of an individual's physiological adaptations to environmental challenges. Differences in stature and body reserves created by the two rearing diets diminished during late gestation and the 5-day control period. Genetic line did not affect body reserves during the rearing phase. Rearing diet and genetic line slightly affected the recovery profiles of evaluated traits and had no effects on prechallenge and response to challenge profiles. The prekidding energy status measures and MY before challenge were selected as strong predictors of variability in response-recovery profiles of milk metabolites that have strong links with body energy dynamics (i.e., isoCitrate, ß-hydroxybutyrate, choline, cholesterol, and triacylglycerols; R2 = 35%). Our results suggested that prekidding energy status and MY are key determinants of adult resilience and that rearing diet and genetic line may affect adult resilience insofar as they affect the animals' energy status.

Responses of selected plasma metabolites to a two-day nutritional challenge of goats divergently selected for functional longevity.

Understanding the extent to which genetics × environment plays a role in shaping individual strategies to environmental challenges is of considerable interest for future selection of more resilient animals. Accordingly, the objective of this study was to evaluate the metabolic responses to a nutritional challenge of goats divergently selected for functional longevity based on plasma metabolites and the repeatability of these responses across 2 experimental farms and years. We carried out 6 different experimental trials from years 2018 to 2022 (4 trials on site Bourges (2018-21) and 2 trials (2021-22) on site Grignon) in which 267 first kidding goats, daughters of Alpine bucks divergently selected for functional longevity, longevity plus (n = 137), and longevity minus (n = 130), were exposed to a 2-d nutritional challenge in early lactation. The experiments consisted of a 5 or 7-d control period (pre-challenge) on a standard lactation diet followed by a 2-d nutritional challenge with straw-only feeding and then a 7 or 10-d recovery period on a standard lactation diet, for site Bourges and Grignon, respectively. During the challenge plasma metabolite composition was recorded daily. Linear mixed-effects models were used to analyze all traits, considering the individual as a random effect and the 2x2 treatments (i.e., genetic line and year nested in site) and litter size as fixed effects. The linear mixed-effects model using a piecewise arrangement was used to analyze the response/recovery profiles to the nutritional challenge. Random parameters estimated for each individual, using the mixed-effects models without the fixed effects of genetic line, were used in a Sparse Partial Least Square Discriminant Analysis (sPLS-DA) to compare the goat metabolism response to the challenge on a multivariate scale. The plasma metabolites, glucose, ß-hydroxybutyrate (BHB), and nonesterified fatty acids (NEFA), and urea concentrations responded to the 2-d nutritional challenge. Selection for functional longevity did not affect plasma glucose, NEFA, BHB, and urea response/recoveries to a 2-d nutritional challenge. However, site, trial, and litter size affected these responses. Moreover, the plasma metabolites seem not to fully recover to prechallenge levels after the recovery phase. The sPLS-DA analysis did not discriminate between the 2 longevity lines. We observed meaningful between-individuals' variability in plasma BHB, especially on the prechallenge and rate of response and rate of recovery from the 2-d nutritional challenge (CV = 26.2%, 36.1%, and 41.2%, repeatability = 0.749, 0.322, and 0.741, respectively). Plasma NEFA recovery from challenge also demonstrated high between-individuals' variability (CV = 16.4%, repeatability = 0.323). Selection for functional longevity did not affect plasma metabolites responses to a 2-d nutritional challenge in dairy goats. Plasma NEFA and BHB response/recovery presented high between-individuals' variability, indicating individual adaptative characteristics to nutritional challenges not related to the environmental conditions but to inherent individual characteristics.

Predictive factors for abscessing tonsillitis: a retrospective analysis.

OBJECTIVE: In clinical practice, identifying abscesses in tonsillar infections is crucial for early therapeutic management. Diagnosis of a peritonsillar abscess is usually based on clinical symptoms. Complementary examination procedures, such as laboratory parameters and imaging, are available for confirmation. PATIENTS AND METHODS: A retrospective analysis was carried out of data for 752 patients who presented with acute tonsillar infection and were hospitalized between January 2012 and February 2021. The data analyses involved evaluating the patient's clinical symptoms, inflammatory parameters, and previous medical history in relation to the predictive power of these factors for the presence of an abscess. RESULTS: Predictor analysis for the presence of an abscess showed significant values for trismus (OR 2.392; 95% CI, 1.305 to 4.383; p=0.005) and palatal arch protrusion (OR 29.679; 95% CI, 17.460 to 50.447; p=0.000). The inflammatory parameter C-reactive protein and the leukocyte count were not statistically significant as predictors. CONCLUSIONS: The presence of a tonsillar abscess can be diagnosed from the clinical presentation alone if the findings are clear. Further diagnostic procedures are indicated in case of inconclusive findings, and ultrasound should be the primary noninvasive method. Computed tomography is only required in selected cases. Inflammatory parameters can be assessed in order to monitor therapy, but do not predict the presence of an abscess. However, if defined action sequences are being considered, tonsillar abscesses can be differentiated at an early point.

Analysis of reproduction success, growth and milk trajectories and response to nutritional challenge in two Alpine goat lines selected on divergent longevity.

This study aims to investigate whether the variation in reproduction success, growth, and milk trajectories is associated with different adaptive strategies in the short term (response to an acute nutritional challenge), using two Alpine goat lines. A total of 382 Alpine goats (179 low longevity (low_LGV) and 203 high longevity (high_LGV)), selected for divergent functional longevity from a commercial population, were monitored for 4 years and recorded for BW, reproduction and milking performance. Every year, an average of fifty primiparous goats were exposed to a 2-d nutritional challenge in early lactation. A polynomial model was used to analyse the lifetime trajectory of lactation and BW. A piecewise model was used to analyse the individual milk yield and responses of milk components to the nutritional challenges. The statistical analysis revealed that the two lines had a similar performance for total milk yield in the first lactation, BW at birth and at first kidding, litter size and weight, kidding interval and interval from the first insemination to conception. BW trajectories revealed that low_LGV goats had a greater BW in pregnancy but then lost more weight in early lactation compared to high_LGV goats, which showed a greater BW after kidding. Milk trajectories showed that the high_LGV goats had a higher initial milk yield, an earlier but less marked lactation peak and more persistency in milk production in late lactation than low_LGV goats. Except for milk protein content, quite similar response and recovery profiles of milk yield and milk fat content were observed during the challenge for both lines. The response to the challenge was positively correlated to the initial level of milk production in early lactation but negatively correlated with milk production decline after the peak. This finding suggests that the low_LGV goats were more adapted to allocate resources to meet an expected physiological change such as gestation and lactation. However, high_LGV goats allocate more than low_LGV goats for structural mass and may better cope with an unexpected environmental change such as nutritional deficit.

Multivariate analysis of milk metabolite measures shows potential for deriving new resilience phenotypes.

In a context of growing interest in breeding more resilient animals, a noninvasive indicator of resilience would be very valuable. We hypothesized that the time-course of concentrations of several milk metabolites through a short-term underfeeding challenge could reflect the variation of resilience mechanisms to such a challenge. We submitted 138 one-year-old primiparous goats, selected for extreme functional longevity (i.e., productive longevity corrected for milk yield [60 low longevity line goats and 78 high longevity line goats]), to a 2-d underfeeding challenge during early lactation. We measured the concentration of 13 milk metabolites and the activity of 1 enzyme during prechallenge, challenge, and recovery periods. Functional principal component analysis summarized the trends of milk metabolite concentration over time efficiently without preliminary assumptions concerning the shapes of the curves. We first ran a supervised prediction of the longevity line of the goats based on the milk metabolite curves. The partial least square analysis could not predict the longevity line accurately. We thus decided to explore the large overall variability of milk metabolite curves with an unsupervised clustering. The large year × facility effect on the metabolite concentrations was precorrected for. This resulted in 3 clusters of goats defined by different metabolic responses to underfeeding. The cluster that showed higher ß-hydroxybutyrate, cholesterol, and triacylglycerols increase during the underfeeding challenge was associated with poorer survival compared with the other 2 clusters. These results suggest that multivariate analysis of noninvasive milk measures show potential for deriving new resilience phenotypes.

EAONO/JOS classification for acquired cholesteatoma: evaluating the impact of the number of affected sites on treatment and outcomes.

PURPOSE: The European and Japanese system for cholesteatoma classification proposed an anatomical differentiation in five sites. In stage I disease, one site would be affected and in stage II, two to five. We tested the significance of this differentiation by analyzing the influence of the number of affected sites on residual disease, hearing ability and surgical complexity. METHODS: Cases of acquired cholesteatoma treated at a single tertiary referral center between 2010-01-01 and 2019-07-31 were retrospectively analyzed. Residual disease was determined according to the system. The air-bone gap mean of 0.5, 1, 2, 3 kHz (ABG) and its change with surgery served as hearing outcome. The surgical complexity was estimated regarding the Wullstein's tympanoplasty classification and the procedure approach (transcanal, canal up/down). RESULTS: 513 ears (431 patients) were followed-up during 21.6 ± 21.5 months. 107 (20.9%) ears had one site affected, 130 (25.3%) two, 157 (30.6%) three, 72 (14.0%) four and 47 (9.2%) five. An increasing number of affected sites resulted in higher residual rates (9.4-21.3%, p = 0.008) and surgical complexity, as well poorer ABG (preoperative 14.1 to 25.3 dB, postoperative 11.3-16.8 dB, p < 0.001). These differences existed between the means of cases of stage I and II, but also when only considering ears with stage II classification. CONCLUSION: The data showed statistically significant differences when comparing the averages of ears with two to five affected sites, questioning the pertinence of the differentiation between stages I and II.

Fluorometric determination of isocitrate dehydrogenase (EC 1.1.1.42; 1; NADP+ dependent) in ruminant milk.

The enzyme isocitrate dehydrogenase (EC 1.1.1.42; 1; NADP+ dependent) located in the mammary cell cytosol mediates the synthesis of the majority of reducing equivalents for the energetically demanding milk fat and cholesterol synthesis in mammary cell cytosol. The present article presents a novel fluorometric method for quantification of the activity of this enzyme (IDH) in ruminant milk without pretreatment of the sample. Further, 493 goat milk samples - harvested before, during and after a nutritional restriction - were analysed for IDH activity i) with addition of extra substrate (isocitrate), and ii) with the intrinsic isocitrate solely. The IDH activity ranged from 0.22 to 15.4 units [nano moles product/(ml * min)] (un-supplemented) and from 0.22 to 45.6 units (isocitrate supplemented). The IDH activity increased considerably in milk during the nutritional restriction period concomitant with the increase in the metabolite isocitrate concentration and somatic cell count and returned to the initial level shortly after restriction period. The present 'high through-put' analytical method may be beneficial in future studies to phenotype modifications in mammary energy metabolism and milk fat synthesis, for which IDH activity may be a biomarker.

Selection on functional longevity in a commercial population of dairy goats translates into significant differences in longevity in a common farm environment.

Resilience is the ability of an animal to cope with environmental disturbances, such as pathogens or negative energy balance. To improve resilience through breeding, we need resilience indicators. Functional longevity might be a good indicator of a dairy goat's lifetime resilience as it results from the ability to cope with and recover from all the challenges faced throughout its lifetime. The aim of this study was to validate the use of functional longevity as an indicator of resilience for selection. To address this question, we created 2 genetic lines of Alpine goats using hyperselected artificial insemination bucks with the most extreme estimated breeding values for functional longevity and the same milk yield performance. A total of 440 goats, 228 in the high longevity (high_LGV) and 221 in the low longevity (low_LGV) lines, were bred and monitored for 4 yr. Health treatments, serum IgG concentration as a proxy of passive immune transfer in early life, kidding, age, and reason of culling were systematically noted. Weight and body morphology were monitored. Weight and growth during the first year of life were similar in both goat lines. In contrast, the low_LGV goats had a lower weight during the beginning of first lactation than high_LGV goats. The milk fat-to-protein ratio was also significantly higher in low_LGV goats during first lactation. A multivariable Cox regression was fitted to the data to decipher survival at different stages of life in the 2 lines. The overall survival of high_LGV goats was significantly better than low_LGV goats (hazard ratio = 0.63, confidence interval = 0.47; 0.86) even after we included treatment, growth, serum IgG concentration at birth, and year effects in the model. The line effect was not constant over time; no significant effect was found during the first year, and the difference was observed after first kidding. This result suggested that survival at an early stage of life and during later productive life are under different genetic regulation. Altogether, this monitoring of the goat lines indicated that functional longevity-based selection helps to improve resilience by improving survival and mitigating some indicators of fat mobilization during early lactation.

Animal Board Invited Review: Meta-analysis of genetic parameters for resilience and efficiency traits in goats and sheep.

Genetic selection focused purely on production traits has proven very successful in improving the productive performance of livestock. However, heightened environmental and infectious disease challenges have raised the need to also improve the resilience of animals to such external stressors, as well as their efficiency in utilising available resources. A better understanding of the relationship between efficiency and production and health traits is needed to properly account for it in breeding programmes and to produce animals that can maintain high production performance in a range of environmental conditions with minimal environmental footprint. The aim of this study was to perform a meta-analysis of genetic parameters for production, efficiency and health traits in sheep and goats. The dataset comprised 963 estimates of heritability and 572 genetic correlations collated from 162 published studies. A threelevel meta-analysis model was fitted. Pooled heritability estimates for milk production traits ranged between 0.27 ± 0.03 and 0.48 ± 0.13 in dairy goats and between 0.21 ± 0.06 and 0.33 ± 0.07 in dairy sheep. In meat sheep, the heritability of efficiency traits ranged from 0.09 ± 0.02 (prolificacy) up to 0.32 ± 0.14 (residual feed intake). For health traits, pooled heritability was 0.07 ± 0.01 (faecal egg count) and 0.21 ± 0.01 (somatic cell score) in dairy goats and 0.14 ± 0.04 (faecal egg count) and 0.13 ± 0.02 (somatic cell score) in dairy sheep. In meat sheep, the heritability of disease resistance and survival traits ranged between 0.07 ± 0.02 (mastitis) and 0.50 ± 0.10 (breech strike). Pooled estimates of genetic correlations between resilience and efficiency traits in dairy goats were not significantly different from zero with the exception of somatic cell score and fat content (-0.19 ± 0.01). In dairy sheep, only the unfavourable genetic correlation between somatic cell score and protein content (0.12 ± 0.03) was statistically significant. In meat sheep only, the correlations between growth and faecal egg count (-0.28 ± 0.11) as well as between growth and dagginess (-0.33 ± 0.13) were statistically significant and favourable. Results of this meta-analysis provide evidence of genetic antagonism between production and health in dairy sheep and goats. This was not observed in meat sheep where most of the pooled estimates had high standard errors and were non-significant. Based on the obtained results, it seems feasible to simultaneously improve efficiency and health in addition to production by including the different types of traits in the breeding goal. However, a better understanding of potential trade-offs between these traits would be beneficial. Particularly, more studies focused on reproduction and resilience traits linked to the animal's multi-trait response to challenges are required.

The COVID-19 pandemic and its consequences for the diagnosis and therapy of head and neck malignancies.

OBJECTIVE: The COVID-19 pandemic and the measures accompanying it have been accused of having a negative influence on the frequency and methods of treatment of various diseases including head and neck cancer (HNSCC). To go further into this assumption, the diagnoses made, and treatments performed at one of Germany's largest head and neck cancer centres were evaluated. PATIENTS AND METHODS: This study consisted of one single centre and involved a retrospective review of all patients with newly diagnosed or recurrent HNSCC. The diagnosis and treatment methods used in the pre-COVID-19 time period between March 1st, 2019, and March 1st, 2020, were analysed and compared with the COVID-19 time period from April 1st, 2020, until April 1st, 2021. The primary objective was defined as the number of malignant diagnoses and the secondary objectives as the disease stage and the time to therapy. RESULTS: A total of 612 patients (160♀; mean 63 yrs.) were included. 319 patients (52%) were treated in the pre-COVID-19 time. The two groups did not differ in terms of age (p=0.304), gender (p=0.941), presence of recurrent disease (p=0.866), tumour subsite (p=0.194) or the duration from presentation to the multidisciplinary tumour board until start of therapy (p=0.202). There were no significant differences in the T stage (p=0.777), N stage (p=0.067) or UICC stage (p=0.922). During the pre-COVID-19 period more patients presented with distant metastases (n= 23 vs. n=8; p=0.011). CONCLUSIONS: This study shows that there was no significant change in either the number and severity of HNSCC diagnoses or the time until start of therapy at this large head and neck cancer centre as a result of the COVID-19 pandemic.

Magnetically tunable optical diffraction gratings based on a ferromagnetic liquid crystal.

Transmission optical diffraction gratings composed of periodic slices of a ferromagnetic liquid crystal and a conventional photoresist polymer are demonstrated. Dependence of diffraction efficiencies of various diffraction orders on an in-plane external magnetic field is investigated. It is shown that diffraction properties can be effectively tuned by magnetic fields as low as a few mT. The tuning mechanism is explained in the framework of a simple empirical model and also by numerical simulations based on the rigorous coupled wave analysis (RCWA). The obtained results provide a proof of principle of operation of magnetically tunable liquid crystalline diffractive optical elements applicable in contactless schemes for control of optical signals.

Divergent selection on milk somatic cell count in goats improves udder health and milk quality with no effect on nematode resistance.

Milk somatic cell count (SCC) is commonly higher in goats than in cattle and sheep. Furthermore, the ability of milk SCC to predict mastitis is considered lower in goats than in cattle and sheep, and the relevance of somatic cell score (SCS)-based selection in this species has been questioned. To address this issue, we created 2 divergent lines of Alpine goats using artificially inseminated bucks with extreme estimated breeding values for SCS. A total of 287 goats, 158 in high- and 129 in low-SCS lines, were scrutinized for mastitis infections. We subjected 2,688 milk samples to conventional bacteriological analyses on agarose and bacterial counts were estimated for positive samples. The SCS, milk yield, fat content, and protein content were recorded every 3 wk. Clinical mastitis was systematically noted. A subset of 40 goats (20 from each line) was subsequently challenged with Haemonchus contortus and monitored for anemia (blood packed cell volume) and fecal egg counts to see if SCS-based selection had an indirect effect on resistance to gastrointestinal nematodes. Milk production traits, including milk quantity, fat content, and protein content, were similar in both goat lines. In contrast, the raw milk SCC almost doubled between the lines, with 1,542,000 versus 855,000 cells/mL in the high- and low-SCS lines, respectively. The difference in breeding value for SCS between lines was 1.65 genetic standard deviation equivalents. The Staphylococcus spp. most frequently isolated from milk were S. xylosus, S. caprae, S. epidermidis, and S. aureus. The frequency of positive bacteriology samples was significantly higher in the high-SCS line (49%) than in the low-SCS line (33%). The highest odds ratio was 3.49 (95% confidence interval: 11.95-6.25) for S. aureus. The distribution of bacterial species in positive samples between lines was comparable. The average quantity of bacteria in positive samples was also significantly higher in high-SCS goats (69 ± 80 growing colonies) than in low-SCS goats (38 ± 62 growing colonies). Clinical cases were rare and equally distributed between high- (n = 4; 2.5%) and low-SCS (n = 3; 2.3%) lines. Furthermore, the larger the amounts of bacteria in milk the higher the SCS level. Conversely, goats with repeatedly culture-negative udders exhibited the lowest SCC levels, with an average of below 300,000 cells/mL. We therefore confirmed that SCS is a relevant predictor of intramammary infection and hygienic quality of milk in goats and can be used for prophylactic purposes. After challenge with H. contortus, goats were anemic with high fecal egg counts but we found no difference between the genetic lines. This result provides initial evidence that resistance to mastitis or to gastrointestinal nematodes infections is under independent genetic regulation. Altogether, this monitoring of the goat lines indicated that SCS-based selection helps to improve udder health by decreasing milk cell counts and reducing the incidence of infection and related bacterial shedding in milk. Selection for low SCC should not affect a goat's ability to cope with gastrointestinal nematodes.

A dose ranging study of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants.

BACKGROUND: Two new formulations of an investigational 15-valent pneumococcal conjugate vaccine (PCV15-A and PCV15-B) were developed using 2 different protein-polysaccharide conjugation processes and evaluated in separate phase I/II studies (NCT02037984 [V114-004] and NCT02531373 [V114-005]) to assess optimal concentrations of pneumococcal polysaccharide (PnPs) and Aluminum Phosphate Adjuvant. METHODS: Various lots of PCV15-A and PCV15-B containing different concentrations of PnPs and/or adjuvant were compared to PCV13 in young adults and infants. Adults received single dose and infants received 4 doses at 2, 4, 6, and 12-15 months of age. Adverse events (AEs) were collected after each dose. Serotype-specific immunoglobulin G (IgG) concentrations and opsonophagocytic activity (OPA) were measured prior and 30 days postvaccination in adults, at 1 month postdose 3 (PD3), pre-dose4, and postdose 4 (PD4) in infants. RESULTS: Safety profiles were comparable across vaccination groups. At PD3, serotype-specific IgG GMCs were generally lower for either PCV15 formulation than PCV13 for most shared serotypes. PCV15 consistently elicited higher antibody responses to the 2 serotypes unique to the vaccine (22F and 33F) and serotype 3 for which PCV13 was shown to be ineffective. Except for serotypes 6A and 6B, no dose-response effect was observed with increasing concentrations of PnPs and/or adjuvant. CONCLUSION: PCV15 is safe and induces IgG and OPA responses to all 15 serotypes in the vaccine. No significant differences in antibody responses were observed with increases in PnPs and/or Aluminum Phosphate Adjuvant.

Invited review: Low milk somatic cell count and susceptibility to mastitis.

An enduring controversy exists about low milk cell counts and susceptibility to mastitis. The concentration of milk leukocytes, or somatic cell count (SCC), is a well-established direct indicator of mammary gland inflammation that is highly correlated with the presence of a mammary infection. The SCC is also used as a trait for the selection of dairy ruminants less prone to mastitis. As selection programs favor animals with less SCC, and as milk cells contribute to the defense of the mammary gland, the idea that susceptibility to mastitis could possibly be increased in the long term has been put forward and is still widely debated. Epidemiological and experimental studies aimed at relating SCC to susceptibility to mastitis have yielded results that seem contradictory at first sight. Nevertheless, by taking into account the immunobiology of milk and mammary tissue cells and their role in the defense against infection, along with recent studies on SCC-based divergent selection of animals, the issue can be settled. Apparent SCC-linked susceptibility to mastitis is a phenotypic trait that may be linked to immunomodulation but not to selection.

Instrumented gait analysis in patients with medial osteoarthritis of the knee after mobile-bearing unicompartmental knee arthroplasty.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) is an effective treatment for patients with medial osteoarthritis of the knee joint. Instrumented gait analysis provides an objective measure to quantify and qualify postoperative changes of gait. The purpose of this study was to evaluate standardized instrumented gait analysis for functional recovery and gait as an outcome of mobile-bearing UKA in patients with medial osteoarthritis of the knee. METHODS: Twenty-one patients with isolated medial osteoarthritis of the knee joint received mobile-bearing UKA. They were examined by a gait analysis before surgery and after an average follow-up time of seven months. Gait analysis was performed on a treadmill with six infrared-cameras to identify changes of gait characteristics (e.g., velocity, stride time, stride length, knee adduction and hip abduction). RESULTS: Mean velocity (chosen by individuals) increased from 0.61 to 0.76m/s and further significant advancements, particularly in the knee adduction and the hip abduction were detected. Time and length of strides improved significantly as well as the clinical scores American Knee Society Score (AKSS), Oxford-12, Hannover Functional Ability Questionnaire for Osteoarthritis (FFbH-OA) Score and Devane Score. CONCLUSION: Mobile-bearing UKA can restore physiological axis of the leg and improve gait and function of the knee joint. The combination of instrumented gait analysis with clinical scores constitutes an eligible measuring instrument to quantify and qualify changes in patients' gait patterns.

Somatic cell count-based selection reduces susceptibility to energy shortage during early lactation in a sheep model.

During the transition from late gestation to early lactation ruminants experience a negative energy balance (NEB), which is considered to increase susceptibility to mammary infections. Our previous study in 2 divergent lines of sheep selected for high and low somatic cell score (SCS) suggested an association between the response to NEB and genetic susceptibility to mastitis. Forty-eight early-lactation primiparous dairy ewes from the 2 SCS genetic lines were allocated to 2 homogeneous subgroups-an NEB group, which was energy restricted and received 60% of the energy requirements for 15 d, and a control-fed group-to obtain 4 balanced groups of 12 ewes: high-SCS positive energy balance, low-SCS positive energy balance, high-SCS NEB, and low-SCS NEB. High-SCS ewes showed greater weight loss and increased plasmatic concentrations of ß-hydroxybutyrate and nonesterified fatty acids than low-SCS ewes when confronted with an induced NEB. The aim of this study was to further characterize this interaction by combining transcriptomic and phenotypic data with a generalized partial least squares discriminant analysis using mixOmics package framework. A preliminary analysis using 3 blocks of phenotypes (fatty acids, weight and production, blood metabolites) revealed a high correlation between fat-to-protein ratio, ß-hydroxybutyrate, and nonesterified fatty acids concentrations with milk long-chain fatty acid yields. These phenotypes allowed good discrimination of the energy-restricted high-SCS ewes and confirmed a high level of adipose tissue mobilization in this group. A second analysis, which included RNA-seq data, revealed high correlations between the long-chain fatty acid yields in milk and PDK4, CPT1A, SLC25A20, KLF10, and KLF11 expression, highlighting the relationship between mobilization of body reserves and enhanced fatty acids utilization for energy production in blood cells. Finally, analysis of milk composition measured in 1,025 ewes from the 2 genetic lines over 10 yr confirmed significant higher fat-to-protein ratio in high-SCS ewes in early lactation. Altogether, our results strongly confirmed a genetic link between susceptibility to mastitis and metabolic adaptation to energy shortage. Improving genetic resistance to mastitis using SCS should be accompanied by a favorable effect on the response to metabolic stress, especially in highly stressful early lactation. Moreover, this study suggests that the fat-to-protein ratio could be used as a low-cost tool for monitoring energy balance and ketosis during this critical phase of lactation.

Spinal cord ability ruler: an interval scale to measure volitional performance after spinal cord injury.

STUDY DESIGN: Retrospective statistical analysis of database. OBJECTIVE: Spinal cord injury (SCI) clinical trials are challenged to enroll participants, and early trial outcomes have often been equivocal. We hypothesized that a specifically designed novel true linear interval-scaled outcome measure targeted to simultaneously track a broad range of SCI will enable more inclusive enrollment of participants and valid comparisons of functional changes after SCI. METHODS: To define a single SCI measurement framework, we used items from existing measures. To evaluate linearity and validity of the measure, we used rigorous psychometric Rasch analysis on two data sets from over 2500 traumatic SCI participants (all levels and severities of SCI) within the EMSCI (European Multicenter study about SCI) database. RESULTS: Volitional performance was found to be the unidimensional construct that would detect and track a treatment effect from a central nervous system-directed therapeutic. Along with early evidence for voluntary neurological control of upper-extremity muscle contractions, volitional performance is best described by goal-directed activities of daily living that are increasingly difficult to re-acquire when activity within more caudal spinal segments is required. Validity of the Spinal Cord Ability Ruler (SCAR) as a linear interval construct was confirmed with Rasch analysis. All measurement items were properly ordered, as well as being precise and stable across clinically relevant groups. Only 5/24 items had some misfit. Targeting was excellent over time after SCI, with few gaps and only modest floor and ceiling effects (3% each). CONCLUSIONS: SCAR is a quantitative linear measure of volitional performance across an inclusive range of tetraplegic and paraplegic SCI.

Validity and reliability of a locomotor stage-based functional rating scale in spinal cord injury.

STUDY DESIGN: This is a prospective observational cohort study. OBJECTIVES: The objectives of this study were to apply and adapt a rating scale based on locomotor stages (LSs) derived from cerebral palsy (CP) to spinal cord injury (SCI) and to quantify its inter-rater reliability and construct validity. METHODS: The inter-rater reliability of LSs originally developed for children with CP was tested in a chronic SCI cohort. On the basis of the distribution of the LSs for CP, Locomotor Stages in Spinal Cord Injury (LOSSCI) were defined. Their validity was then tested with the Spinal Cord Independence Measure (SCIM) in another acute SCI cohort. RESULTS: The 10-point LSs for CP were assessed by two raters in 65 chronic patients. Weighted Cohen's kappa (WCk) was 0.985 (P<0.0001). Only four mismatches were found, resulting in an accuracy of 93.4%. On the basis of the distribution of the LSs for CP in SCI, the five-point LOSSCI grading scale was developed. WCk of LOSSCI was 0.976 (P<0.0001). Only three mismatches between raters were found, resulting in an overall accuracy of 95.1%. The validity data sets consisted of 448 SCIM records from 161 patients obtained within the first year after injury. Spearman's correlation coefficients were the highest between LOSSCI and SCIM indoor mobility (room and toilet; R=0.82) and the lowest between LOSSCI and SCIM respiration and sphincter management (R=0.68). CONCLUSION: LOSSCI provides a reliable and valid clinical tool to assess locomotor function in SCI. LOSSCI not only reflects bipedal walking but also covers a wide range of key motor skills.

Response to dietary-induced energy restriction in dairy sheep divergently selected for resistance or susceptibility to mastitis.

Dairy ruminants experiencing a severe postpartum negative energy balance (NEB) are considered to be more susceptible to mastitis. Although the genetic variability of mastitis resistance is well established, the biological basis of the link between energy metabolism and resistance is mostly unknown. The aim of this study was to characterize the effect of NEB on metabolism and immune response according to the genetic background for mastitis resistance or susceptibility. Forty-eight ewes from high and low somatic cell score (SCS) genetic lines were allocated to 2 homogeneous subgroups 2 wk after lambing: one group (NEB) received an energy-restricted diet to cover 60% of their energy requirements, and the other group received a control (positive energy balance: PEB) diet. Both diets met the protein requirements. After 10 d on either the NEB or PEB diet, all ewes were injected with a Pam3CSK4/MDP solution in one half-udder to induce an inflammatory response. The ewes were monitored for milk production, somatic cell count (SCC), body weight (BW), body condition score (BCS), and blood metabolites. Differential milk cell counts were determined by flow cytometry. Plasma concentrations of glucose, insulin, nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), and triiodothyronine were determined. Energy restriction resulted in an increased fat:protein ratio in milk and decreased milk yield, BW, and BCS. The NEB ewes had significantly higher NEFA and BHB and lower plasma glucose concentrations than PEB ewes, reflecting a mobilization of body reserves and ketone body synthesis. High-SCS ewes had a higher SCS than low-SCS throughout the experiment, except after the inflammatory challenge, which resulted in similar SCS in all 4 groups. A noteworthy interaction between genetic background and diet was evidenced on metabolic parameters and BW. Indeed, high-SCS ewes subjected to NEB showed greater decrease in BW and increased NEFA and BHB concentrations compared with low-SCS ewes. Thus, NEB in early lactation led to extensive mobilization of body reserves and intense ketone body synthesis in mastitis-susceptible sheep. These results reinforce the hypothesis of a genetic association between mastitis susceptibility and energy metabolism and open the way to further studies on the biological basis for this association.

Steer by ear: Myoelectric auricular control of powered wheelchairs for individuals with spinal cord injury.

PURPOSE: Providing mobility solutions for individuals with tetraplegia remains challenging. Existing control devices have shortcomings such as varying or poor signal quality or interference with communication. To overcome these limitations, we present a novel myoelectric auricular control system (ACS) based on bilateral activation of the posterior auricular muscles (PAMs). METHODS: Ten able-bodied subjects and two individuals with tetraplegia practiced PAM activation over 4 days using visual feedback and software-based training for 1 h/day. Initially, half of these subjects were not able to voluntarily activate their PAMs. This ability was tested with regard to 8 parameters such as contraction rate, lateralized activation, wheelchair speed and path length in a virtual obstacle course. In session 5, all subjects steered an electric wheelchair with the ACS. RESULTS: Performance of all subjects in controlling their PAMs improved steadily over the training period. By day 5, all subjects successfully generated basic steering commands using the ACS in a powered wheelchair, and subjects with tetraplegia completed a complex real-world obstacle course. This study demonstrates that the ability to activate PAM on both sides together or unilaterally can be learned and used intuitively to steer a wheelchair. CONCLUSIONS: With the ACS we can exploit the untapped potential of the PAMs by assigning them a new, complex function. The inherent advantages of the ACS, such as not interfering with oral communication, robustness, stability over time and proportional and continuous signal generation, meet the specific needs of wheelchair users and render it a realistic alternative to currently available assistive technologies.