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International audience; Fertility is of primary economic importance in dairy cattle and the most common reason for involuntary culling. However, standard fertility traits have very low heritability that renders genetic selection slow and difficult. In this study, we explored fertility from an endocrine standpoint. A total of 1,163 crossbred Holstein-Normande females in a 3-generation familial design were studied for progesterone level measured every 10 d to determine age at puberty (PUB) and commencement of postpartum luteal activity (CPLA). Genetic parameters were estimated using REML with WOMBAT software. The heritability estimates were 0.38 ± 0.10 and 0.16 ± 0.07 for PUB and CPLA, respectively. Moreover, the 2 traits were genetically correlated (0.45 ± 0.23), suggesting a partially common determinism. Because of the family structure, a linkage disequilibrium and linkage analysis approach was preferred over standard genome-wide association study to map genomic regions associated with these traits. Ten quantitative trait loci (QTL) were detected for PUB on chromosomes 1, 3, 11, 13, 14, 21, and 29, whereas 3 QTL were associated with CPLA on chromosomes 21 and 26. Only the QTL on chromosome 21 was common to both traits. Four functional candidate genes (NCOA2, GAS2, OVOL1, and FOSL1) were identified in the detected regions. These findings will contribute to a clearer understanding of fertility determinism and enhance the value of introducing endocrinological data in fertility studies.

Recent developments in multiplex technologies enable the determination of a large nu\mber of soluble proteins such as cytokines in various biological samples. More than a one-by-one determination of the concentration of immune mediators, they permit the establishment of secretion profiles for a more accurate description of conditions related to infectious diseases or vaccination. Cytokine profiling has recently been made available for bovine species with the development of a Luminex® technology-based 15-plex assay. Independently from the manufacturer, we evaluated the bovine cytokine/chemokine multiplex assay for limits of detection, recovery rate, and reproducibility. Furthermore, we assessed cytokine secretion in blood samples from 107 cows upon stimulation with heat-killed bacteria and TLR2/4 ligands compared to a null condition. Secretion patterns were analyzed either using the absolute concentration of cytokines or using their relative concentration with respect to the overall secretion level induced by each stimulus. Using Partial Least Square-Discriminant Analysis, we show that the 15-cytokine profile is different under Escherichia coli, Staphylococcus aureus, and Streptococcus uberis conditions, and that IFN-γ, IL-1β, and TNF-α contribute the most to differentiate these conditions. LPS and E. coli induced largely overlapping biological responses, but S. aureus and S. uberis were associated with distinct cytokine profiles than their respective TLR ligands. Finally, results based on adjusted or absolute cytokine levels yielded similar discriminative power, but led to different stimuli-related signatures.

A horseshoe abscess is caused by infection that spreads between the flexor tendon sheath of the thumb or little finger through the radial and ulnar bursae through communication between the two and/or the space of Parona. We present a case of an 80-year-old woman with rheumatoid arthritis who presented with 6 months of right hand and wrist soft tissue swelling, initially treated as a rheumatoid arthritis flare. MRI demonstrates the horseshoe abscess and after surgical irrigation and debridement with synovectomy, cultures demonstrated infection with mycobacterium avium intracellulare (MAI). This case demonstrates the importance of MRI in diagnosing and evaluating the extent of hand infections and for considering mycobacterial organisms for appropriate treatment and antibiotic regimen.

In distal upper extremity surgeries, there can be a choice to use an upper arm or forearm tourniquet. This study examines discomfort and tolerance in healthy volunteers to determine whether one is more comfortable.Forty healthy, study participants were randomized to an upper extremity laterality and site. Tourniquets were inflated to 100 mm Hg over systolic blood pressure. Participants experienced an upper arm and a forearm tourniquet sequentially. Visual analog scores (VAS) were recorded at 2-minute intervals. Time until request and VAS at tourniquet deflation were recorded. Time until the complete resolution of paresthesias was also recorded. Participants subjectively stated which tourniquet felt more comfortable.Tourniquets were inflated longer on the forearm than the upper arm (mean 16.1 minutes versus 12.2 minutes; P0.0001). VAS at tourniquet removal was not different between the sites (means 7.3 and 7.3) (P = 0.839). Time until paresthesia resolution after the tourniquet was deflated was not different (means 8.1 and 7.7 minutes) (P = 0.675). Time until paresthesia resolution was proportional to tourniquet inflation time for both sites (regression coefficient 0.41; P0.00001). Participants found the forearm more comfortable (95% confidence interval, 0.63 to 0.92).Forearm placement allows the tourniquet to be inflated for an average of 4 minutes longer. Forearm tourniquet is subjectively more comfortable.

Introduction Necrotizing soft tissue infection (NSTI) of the upper extremity (UE) is a rapidly progressing infection that requires early diagnosis and emergent treatment to decrease risks of loss of limb or life. Clinical presentation, particularly of early NSTI, can appear similar to serious cellulitis or abscess. The purpose of this study was to identify factors that are associated with NSTI rather than serious cellulitis and abscess to differentiate patients with similar clinical presentations. Methods This study uses a retrospective cohort design that compares patients ultimately diagnosed with UE NSTI versus those diagnosed with UE serious cellulitis or abscess. Cohorts were matched using the Laboratory Risk Indicators for Necrotizing Fasciitis (LRINEC) score in the setting of UE soft tissue infection. Laboratory values, vital signs, subjective symptoms, and social factors including substance abuse and domiciled status were recorded. Continuous variables were compared using the Mann-Whitney U test, whereas categorical variables were compared using the chi-squared test or the Fisher exact test (for expected values less than 5). A binary logistic regression for continuous and categorical variables was also performed. Significance was set at p

Introduction The mainstay of trigger finger treatment is a corticosteroid injection of the affected digits and is associated with a very high success rate. However, some patients do not respond to nonsurgical management and undergo subsequent surgical release. The purpose of this study is to investigate the comorbidities that predispose patients to progressing from injection to surgical release. Methods Patient data were obtained from a national insurance database. All patients aged 20 years or older who underwent trigger digit injection were included. Any injection that did not specify the digit was excluded. Subsequent procedures, including repeat injection and surgical release, were identified using relevant Current Procedural Terminology codes. A multivariate model was constructed to evaluate potential risk factors for requiring release after prior injection of the same digit. Stepwise backward selection was used to retain significant variables. Results A total of 42,537 trigger digits were identified in 31,830 patients, most of whom were female. The right hand was affected more commonly than the left. The middle and ring fingers were the most commonly affected digits. Over 80% of all trigger digits underwent only a single injection, and approximately 90% of injected digits did not require subsequent release. In the multivariate model, factors associated with higher risk of release were male sex, involvement of additional digits, multiple injections of the same digit, chronic pulmonary disease, HIV/AIDS, obesity, alcohol abuse, and depression. The model also found small fingers to be less likely to progress to release. Discussion Patients with the risk factors identified in this study are more likely to progress to surgical release after trigger finger injection. Although prospective studies are required, the information may be beneficial in counseling patients and their treatment options.

Background and Aims: There are approximately 1 million total knee arthroplasty (TKA) and total hip arthroplasty (THA) procedures performed annually in the United States. With this number projected to increase, it is vital for orthopedic surgeons and health-care systems to properly anticipate healthcare utilization related to TKA and THA. Google Trends (GT) is a free, open source tool that provides customizable analysis of search terms entered into the Google search engine. We aim to explore the relationship between public interest in TKA and THA as determined by GT data and volume of TKA and THA procedures. Methods: GT data were compiled for ten search terms related to TKA and ten search terms related to THA from January 2009 to December 2017. Annual case volumes for TKA/THA procedures were obtained from the Healthcare Cost and Utilization Project National Inpatient Sample from 2009 to 2017. Trend analysis was performed using univariate linear regression of GT data and TKA/THA case volumes. Results: There was a statistically significant positive correlation between GT data and procedure volume for 14 of the 20 search terms studied. Seven TKA-related search terms with a positive correlation to procedure volumes include “total knee replacement,” “knee replacement,” “knee osteoarthritis,” “knee ache,” “knee swelling,” “knee stiffness,” and “chronic knee pain.” Seven THA-related search terms with a positive correlation to procedure volumes include “hip arthroplasty,” “total hip replacement,” “hip replacement,” “hip osteoarthritis,” “hip ache,” “hip swelling,” and “chronic hip pain.” Conclusion: GT may provide a high utility as a convenient and informative data set for orthopedic surgeons to analyze public interest in TKA and THA procedures. The data provided by GT have the potential to provide real-time, actionable information that may help surgeons and health systems to characterize public interest in TKA and THA and to best identify and address patient needs. Relevance for Patients: The GT tool can be used to measure public interest in TKA/THA, which can inform physician expectations for the patient encounter and lead to the creation of decision aids that better inform the public about the risks and benefits of TKA/THA.

Introduction Precautions issued by organizations such as the American Academy of Orthopaedic Surgeons (AAOS) recommending against any elective, or non-essential, surgical procedures have significantly affected healthcare resource utilization by the public during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this study, we demonstrate the value of the Google Trends (GT) interface to characterize and monitor in real-time the response in public interest toward various elective orthopedic procedures. Methods Search volume databases were generated from January 2015 to May 2020 for keywords related to anterior cruciate ligament (ACL) reconstruction, elbow arthroplasty, hip arthroplasty, knee arthroplasty, and rotator cuff repair. To measure the immediate effects on public interest, the percent change was calculated from the AAOS, and Centers for Medicare and Medicaid Services (CMS) defined a 30-day pre-recommendations period to a 30-day post-recommendations period. To measure long-term effects, mean search volumes from January 1, 2015, to February 29, 2020, were compared to mean search volumes from March 1, 2020, to May 21, 2020. Results In the 30-day period following statements by the AAOS and CMS, interest in all search terms except "partial knee arthroplasty" decreased as follows: "ACL reconstruction" (-32.7%); "ACL repair" (-22.6%); "anterior cruciate ligament reconstruction" (-39.8%); "elbow arthroplasty" (-17.2%); "elbow joint replacement" (-15.1%); "total elbow arthroplasty" (-40.0%); "hip arthroplasty" (-23.0%); "hip replacement" (-41.2%); "total hip arthroplasty" (-23.0%); "knee arthroplasty" (-43.0%); "total knee arthroplasty" (-33.3%); "rotator cuff repair" (-34.2%); "rotator cuff surgery" (-50.6%); "shoulder arthroplasty" (-26.7%). Discussion GT data have previously demonstrated utility in characterizing and anticipating shifts in real-world healthcare utilization, making it an invaluable tool for physicians to anticipate and address the emerging needs of our patient population. Our study further illustrates the value of GT in localizing rapidly recovering interest in several of the most common elective orthopedic surgeries, enabling surgeons with up-to-date actionable data to guide the management of practices and healthcare facilities as the US slowly emerges from precautions endorsed during the COVID-19 pandemic.

Background Over the last years, genome-wide association studies (GWAS) based on imputed whole-genome sequences (WGS) have been used to detect quantitative trait loci (QTL) and highlight candidate genes for important traits. However, in general this approach does not allow to validate the effects of candidate mutations or determine if they are truly causative for the trait(s) in question. To address these questions, we applied a two-step, within-breed GWAS approach on 15 traits (5 linked with milk production, 2 with udder health, and 8 with udder morphology) in Montbéliarde (MON), Normande (NOR), and Holstein (HOL) cattle. We detected the most-promising candidate variants (CV) using imputed WGS of 2515 MON, 2203 NOR, and 6321 HOL bulls, and validated their effects in three younger populations of 23,926 MON, 9400 NOR, and 51,977 HOL cows. Results Bull sequence-based GWAS detected 84 QTL: 13, 10, and 30 for milk production traits; 3, 0, and 2 for somatic cell score (SCS); and 8, 2 and 16 for udder morphology traits, in MON, NOR, and HOL respectively. Five genomic regions with effects on milk production traits were shared among the three breeds whereas six (2 for production and 4 for udder morphology and health traits) had effects in two breeds. In 80 of these QTL, 855 CV were highlighted based on the significance of their effects and functional annotation. The subsequent GWAS on MON, NOR, and HOL cows validated 8, 9, and 23 QTL for production traits; 0, 0, and 1 for SCS; and 4, 1, and 8 for udder morphology traits, respectively. In 47 of the 54 confirmed QTL, the CV identified in bulls had more significant effects than single nucleotide polymorphisms (SNPs) from the standard 50K chip. The best CV for each validated QTL was located in a gene that was functionally related to production (36 QTL) or udder (9 QTL) traits. Conclusions Using this two-step GWAS approach, we identified and validated 54 QTL that included CV mostly located within functional candidate genes and explained up to 6.3% (udder traits) and 37% (production traits) of the genetic variance of economically important dairy traits. These CV are now included in the chip used to evaluate French dairy cattle and can be integrated into routine genomic evaluation.

Background:. The treatment of postoperative, painful sensory neuromas is an ongoing challenge for surgeons. Here, we describe a technique for treatment with excision and allograft reconstruction and report on early results of its use in treating painful saphenous neuromas after knee arthroscopy. Methods:. A retrospective review of a single surgeon’s peripheral nerve clinic from January 1, 2013, to December 31, 2019, was conducted to identify post-knee arthroscopy saphenous neuroma cases in which reconstruction with processed human nerve allograft distally implanted into healthy muscle belly was performed. We examined the outcomes for each patient, including subjective pain self-assessment and need for further surgical treatment. Results:. In total, 9 cases were identified, with patient ages ranging from 21 to 74 years. The average time to referral to peripheral nerve clinic was 31 months (range: 4–143 months). Upon exploration, all nerves were found to have a neuroma in continuity. Six of the 9 patients reported subjective improvement through final follow-up. Three of the 9 patients reported initial improvement, with recurrence of pain at/near the site of the neuroma. The average follow-up time was 9 months (range: 1–21 months). Conclusions:. Here, we report on a novel technique of using a processed human nerve allograft after neuroma resection to provide an organized environment for bridging regenerated axons into muscle tissue. We also describe our early results using this technique to treat iatrogenic saphenous neuromas after knee arthroscopy. Results are encouraging, with 6 of the 9 patients experiencing subjective reduction in pain at final follow-up.

Bone defects may occur after trauma, infection, or oncologic resection. A critical sized defect is any defect that is unable to spontaneously heal and will require secondary procedure(s) to obtain union. Autologous grafting is widely used, but may be insufficient to obtain union in these situations. Other options include the induced membrane technique, bone transport through distraction osteogenesis, or free vascularized bone transfer. This chapter will review options for obtaining graft, and the aforementioned special techniques for managing these challenging problems.

International audience; Evaluation of the immune status must be assessed in highly controlled conditions to be amenable for reproducibility. Furthermore, whereas the cellular response plays a major role, immunity has been measured for a long time through antibody production. For the purpose of assessing immune cell responsiveness in ruminants, we developed and validated a whole blood assay coupled to a high-throughput multiplex cytokine assay using the Luminex technology. A custom Milliplex assay was developed with MERCKMillipore company for the measurement of 15 bovine/ovine cytokines of both the innate and adaptive immunity, and chemokines. Whole blood samples were collected from 110 dairy cows in an INRA experimental unit, and immediately stimulated during 24 hours with heat-killed bacteria (Escherichia coli, Staphylococcus aureus, and Streptococcus uberis), Toll-like receptor ligands (FSL-1 for TLR2, LPS for TLR4, and Gardiquimod for TLR7-8), or soluble anti-CD3/CD28 monoclonal antibodies. Cytokine secretion was determined and compared with a sample prepared in the same condition but without any stimulant. Using ANOVA and data mining methods (PCA, clustering…), we showed that the protocol is able to detect differences between bacteria, with S. uberis being the most potent to induce a response, compared to S. aureus and E. coli that were distinct but more closely related to each other. Similarly, TLR ligands could be distinguished, and Gardiquimod was significantly different from the MyD88- associated TLR2/4-activating ligands. LPS and E. coli provided very similar response profiles confirming previous data indicating that a large part of the E. coli response is mediated through LPS signaling. A high variability of response was detected amongst cattle suggesting environmental and genetic variations of the cytokine response. Altogether, results indicate that cytokine profiling in cattle is achievable and can be used in further work to delineate more precisely the responsiveness of cattle in various situations, including variability of the genetic background.

International audience; We scanned the genome of 77,815 Normande cattle with different Illumina SNP chips (Illumina Inc., San Diego, CA) to map recessive embryonic lethal mutations using homozygous haplotype deficiency. We detected 2 novel haplotypes on chromosomes 11 and 24 but did not confirm 6 previously reported haplotypes. The one on chromosome 11 showed a marked reduction in conception rates and moderate decrease in nonreturn rate in at-risk versus control mating, supporting late embryonic mortality. After fine mapping and analyzing whole-genome sequences, we prioritized a missense mutation in CAD (g.72399397T>C; p.Tyr452Cys)—a gene encoding a protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) essential for de novo pyrimidine biosynthesis—as a candidate causal variant. This transition mutation replaces a tyrosine residue, which is perfectly conserved among living organisms, with a cysteine residue in the carbamoyl-phosphate synthetase 2 domain of the protein. A single animal was confirmed to be homozygous for the mutation based on Sanger sequencing. However, large-scale genotyping of the candidate variant with the Illumina EuroG10k BeadChip revealed an absence of live homozygotes in a panel of 33,323 Normande animals and an absence of carriers in 348,593 animals from 19 other cattle breeds. These results support recessive embryonic lethality with nearly complete penetrance, as was previously reported in CAD mutants in several eukaryote species. The only homozygous cow had extremely poor udder conformation, suggesting a potential role of CAD in udder development, but no effect was detected when comparing daughter yield deviations of 250 heterozygous bulls with that of 2,912 homozygotes for the ancestral allele. Together, our results showed the importance of large-scale screening for homozygous haplotype deficiency with hundreds of thousands of animals, validating results with an independent data set, and considering unexpected live homozygotes, to avoid both false-positive and false-negative discoveries. These discoveries will be used primarily in mating decisions to avoid at-risk mating. In addition, we recommend including CAD in the breeding objectives of Normande cattle.

International audience; Milk spontaneous lipolysis (SL) of milk triglycerides is induced by the lipoprotein lipase, a milk native enzyme, and leads to an accumulation of partial glycerides and free fatty acids that are responsible for the deterioration of the taste of milk products. The gene coding for diacylglycerol acyltransferase 1 (DGAT1), an enzyme implicated in triglycerides synthesis, has an important polymorphic site at the K232A locus. This gene is well known to modulate milk composition. No data are available on the effects of DGAT1 on SL. Thus, a trial was carried out to evaluate the effects of DGAT1 K232A polymorphism on milk SL upon milking frequency variations [once- (ODM) and twice-daily milking (TDM)]. Twenty-one cows were divided into 3 groups according their DGAT1 K232A genotype: 8 cows had the KK genotype of DGAT1 (KK cows), 8 had the KA genotype (KA cows), and 5 had the AA genotype (AA cows). The trial consisted in 3 successive periods: 3 wk of TDM, 3 of ODM, and 4 of TDM. Samples were collected for fat and protein contents, SL, fatty acid, and protein profiles determinations. The KK cows presented higher fat and protein contents, lower milk production, and higher κ-casein percentage. No significant difference in fatty acid composition was noted between groups. The SL was twice as high for KK cows in TDM situations (1.13 vs. 0.59 and 0.63 mEq/100 g of fat, respectively, for KK, KA, and AA cows during the first period of TDM, and 0.46 vs. 0.25 and 0.21 mEq/100 g of fat, respectively, for KK, KA, and AA during the second period of TDM). The SL remained sharply lower in TDM2 than in TDM1. During ODM, no difference in SL was found between groups and SL remained below 0.2 mEq/100 g of fat. These results demonstrate the existence of a correlation between DGAT1 genotypes and spontaneous lipolysis, in interaction with an environmental factor, milking frequency, although it has not been possible to clarify the causal mechanism at this stage.

Background: There is no current literature examining iatrogenic nerve injury resulting from orthopedic procedures across subspecialties and anatomic areas. This study uses a single peripheral nerve surgeon’s experience to investigate the variable time to presentation of adult patients with iatrogenic nerve injury after orthopedic surgery. Methods: A retrospective review of patients examined in Peripheral Nerve Clinic (PNC) from January 1, 2012, to April 1, 2018, at a single, private, university hospital was performed. Fifty-eight adult patients met inclusion criteria. Charts were reviewed to determine the index orthopedic procedure, peripheral nerve affected, clinical deficits, patient demographics, and time from injury to PNC presentation. Results: The average patient age was 51.2 years, and the average time to PNC referral was 10.9 months after the procedure that resulted in nerve injury. The orthopedic procedures included fracture fixation (13), joint arthroplasty (10) knee arthroscopy and ligament reconstruction (9), mass excision (9), shoulder arthroscopy (7), irrigation and debridement (2), removal of deep hardware (2), tendon procedures (2), trigger digit release (2), nerve decompression (1), and release of exertional compartment syndrome (1). Time from injury to PNC presentation was substantially shorter for patients with upper extremity versus lower extremity deficits (5.9 months vs 19.8 months; P = 0.0173) and for patients with motor nerve involvement versus those with isolated sensory nerve injury (4.5 months vs 24.3 months; P = 0.0164). Conclusions: Iatrogenic nerve injury is a risk across orthopedic subspecialties. Nerve injuries in the lower extremity and those with isolated sensory deficits have significantly delayed time to subspecialty presentation.

Background Implantable devices offer convenient, long-acting, and reversible contraception. Injury to the peripheral nerves and blood vessels have been reported as rare complications of implantation and extraction. Case presentation We present a case of ulnar nerve injury in a 21-year-old woman from attempted in-office removal of a deeply implanted Nexplanon® device. The injury resulted in an ulnar nerve palsy requiring surgical exploration, neuroma excision, and sural nerve cable grafting. Conclusions In-office attempts to remove contraceptive implants that are deep or have migrated can cause iatrogenic nerve injury. Devices that are non-palpable, deep, or migrated should be imaged before formal surgical exploration and removal. Any patient with neurologic symptoms after placement or after attempted removal requires prompt diagnosis and referral to a peripheral nerve surgeon.

Background. Dorsal spanning plate fixation is an increasingly popular method of fixation for certain distal radius fractures. Published outcomes are encouraging, but complications are still reported. Methods. We present a case report of a 26-year-old woman with spanning plate breakage and extensor pollicis longus (EPL) metallosis, fraying, and near-complete rupture. The patient’s unsuccessful follow-up led to this complication. Metallosis and damage to the extensor indices (EI) and distal extensor carpi radialis longus (ECRL) were intraoperative obstacles for tendon transfer to restore EPL function. Results. Tendon transfer in the setting of bridge plate failure has not yet been described in the literature. There are reports of spanning plate failure indicating that breakage often happens through the plate’s holes and after fracture healing. Conclusions. The compounded complication of plate failure with extensor tendon injury emphasizes the important relationship between the local anatomy, barriers to patient care, and potential problems after spanning plate fixation.

International audience; Despite its potential utility for predicting cows' milk yield responses to once-daily milking (ODM), the genetic basis of cow milk trait responses to ODM has been scarcely if ever described in the literature, especially for short ODM periods. This study set out to (1) estimate the genetic determinism of milk yield and composition during a 3-wk ODM period, (2) estimate the genetic determinism of milk yield responses (i.e., milk yield loss upon switching cows to ODM and milk yield recovery upon switching them back to twice-daily milking; TDM), and (3) seek predictors of milk yield responses to ODM, in particular using the first day of ODM. Our trial used 430 crossbred Holstein × Normande cows and comprised 3 successive periods: 1 wk of TDM (control), 3 wk of ODM, and 2 wk of TDM. Implementing ODM for 3 wk reduced milk yield by 27.5% on average, and after resuming TDM cows recovered on average 57% of the milk lost. Heritability estimates in the TDM control period and 3-wk ODM period were, respectively, 0.41 and 0.35 for milk yield, 0.66 and 0.61 for milk fat content, 0.60 and 0.80 for milk protein content, 0.66 and 0.36 for milk lactose content, and 0.20 and 0.15 for milk somatic cell score content. Milk yield and composition during 3-wk ODM and TDM periods were genetically close (within-trait genetic correlations between experimental periods all exceeding 0.80) but were genetically closer within the same milking frequency. Heritabilities of milk yield loss observed upon switching cows to ODM (0.39 and 0.34 for milk yield loss in kg/d and %, respectively) were moderate and similar to milk yield heritabilities. Milk yield recovery (kg/d) upon resuming TDM was a trait of high heritability (0.63). Because they are easy to measure, TDM milk yield and composition and milk yield responses on the first day of ODM were investigated as predictors of milk yield responses to a 3-wk ODM to easily detect animals that are well adapted to ODM. Twice-daily milking milk yield and composition were found to be partly genetically correlated with milk yield responses but not closely enough for practical application. With genetic correlations of 0.98 and 0.96 with 3-wk ODM milk yield losses (in kg/d and %, respectively), milk yield losses on the first day of ODM proved to be more accurate in predicting milk yield responses on longer term ODM than TDM milk yield.

We investigated the effect of maternal sire on early pregnancy failure (between D0, day of insemination and D90) in their progeny during the first and second lactations (n=3508) in the Holstein breed. The estimated breeding value (EBV) for cow fertility of 12 bulls (reliability⩾0.95) was used to create the following three groups: low, medium and high EBV (EBV from −0.7 to 1 expressed as genetic standard deviation relative to the mean of the breed). In their daughters (93 to 516 per bull), progesterone measurement was carried out on the day of artificial insemination (AI; D0) to check whether the cows were in the follicular phase and on D18 to 25 to assess non-fertilisation-early embryonic mortality (NF-EEM). Late embryonic mortality (LEM) and early foetal death (FD) were determined by ultrasonography on D45 and D90 and by the return to oestrus after the first AI. Frequencies of NF-EEM, LEM, FD and pregnancy were 33.3%, 11.7%, 1.4% and 48.5% and incidences were 35.1, 19.0, 2.7 and 51.1, respectively. Sire EBV was significantly related to the incidences of pregnancy failure between D0 and D90, fertilisation failure-early embryonic mortality (FF-EEM) and LEM but not to the incidence of FD between D45 and D90 of pregnancy. The relative risk (RR) of FF-EEM was significantly higher (RR=1.2; P

Using a combination of data from the BovineSNP50 BeadChip SNP array (Illumina, San Diego, CA) and a EuroGenomics (Amsterdam, the Netherlands) custom single nucleotide polymorphism (SNP) chip with SNP pre-selected from whole genome sequence data, we carried out an association study of milking speed in 32,491 French Holstein dairy cows. Milking speed was measured by a score given by the farmer. Phenotypes were yield deviations as obtained from the French evaluation system. They were analyzed with a linear mixed model for association studies. We identified SNP on 22 chromosomes significantly associated with milking speed. As clinical mastitis and somatic cell score have an unfavorable genetic correlation with milking speed, we tested whether the most significant SNP on these 22 chromosomes associated with milking speed were also associated with clinical mastitis or somatic cell score. Nine hundred seventy-one genome-wide significant SNP were associated with milking speed. Of these, 86 were associated with clinical mastitis and 198 with somatic cell score. The most significant association signals for milking speed were observed on chromosomes 7, 8, 10, 14, and 18. The most significant signal was located on chromosome 14 ( ZFAT gene). Eleven novel milking speed quantitative trait loci (QTL) were observed on chromosomes 7, 10, 11, 14, 18, 25, and 26. Twelve candidate SNP for milking speed mapped directly within genes. Of these 10 were QTL lead SNP, which mapped within the genes HMHA1 , POLR2E , GNB5 , KLHL29 , ZFAT , KCNB2 , CEACAM18 , CCL24 , and LHPP . Limited pleiotropy was observed between milking speed QTL and clinical mastitis.

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Starving T Cells The T H 17 lineage of CD4 + helper T cells, characterized by the ability to secrete IL-17, is an important mediator of inflammation and autoimmunity. Dampening the responses of these cells or inhibiting their differentiation is of great therapeutic interest. Sundrud et al. (p. 1334 ; see the Perspective by Blander and Amsen ) now show that the small molecule halofuginone inhibits the differentiation of T H 17 cells but not other CD4 + T cell helper lineages both in vitro and in a mouse model of multiple sclerosis. This selective inhibition was mediated by activation of the amino acid starvation response. Amino acid depletion mimicked the effects of halofuginone, whereas excess amino acids rescued T H 17 differentiation. The results highlight the importance of amino acid metabolism in regulating inflammation.

This report will describe clinical experience using risperidone in substance-dependent patients with bipolar disorder. Method. Thirty-six male patients with SUD and bipolar disorder (DSMIII-R), who were admitted to a voluntary, post-detoxification, intermediatecare inpatient substance abuse program, were assessed weekly using the Clinical Global Impressions scale to assess overall functioning. All patients were treated with risperidone (mean dose 2.3 mg/day) in an open-label, naturalistic trial. 20 Results. Of the 36 patients, 11 dropped out before a follow-up appointment. Twenty patients (56%) reported improved or much improved on the CGI scale, and 5 (%) were rated unchanged. Conclusion. The results of this observational trial suggest that risperidone is moderately effective and well tolerated in bipolar patients with substance use disorders and comorbid psychiatric illnesses. In the short-term, risperidone treatment may also contribute to the likelihood of completing substance abuse treatment.

Herd fertility is a key factor for the sustainability of cattle farming. However, declining fertility has become one of the main causes of culling and replacement of cows in developed countries. Omics technologies have been successfully developed in cattle, refining our knowledge of molecular mechanisms governing cattle reproduction. However, most studies have failed to establish clear links between the genome and final phenotypes. Further studies will be needed to integrate all Omics data and develop a systems biology modeling approach to tackle this complex biological function.

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Baseline assessment in a multisite alcohol-dependence treatment study has several purposes: addressing inclusion/exclusion criteria and characterizing participants to illuminate subsequent efficacy and safety patterns of the interventions. Combination pharmacotherapy and behavioral therapy trials, however, require more complex assessments than single-modality studies. Medication trials require measures of initial safety for study drug as well as for subsequent side-effect and adverse-effect monitoring (e.g., physical examination, laboratory markers, somatic symptoms, medical conditions and concomitant medications). Behavioral therapy trials (and in some cases medication trials) warrant baseline measurement of mediators of therapy effect (e.g., prior treatment history, motivation for change, self-efficacy, other psychiatric conditions, treatment expectations and network supports). Measures may be needed to interpret interactions that may be discovered between these modalities.The National Institute on Alcohol Abuse and Alcoholism COMBINE Study evaluated the potentially overwhelming number of candidate instruments through an iterative process, using the following sequence to finalize a rational baseline assessment battery: key constructs, representative measures, determination of duration of assessment, risk of assessment reactivity, goal priorities, necessity for measure "pruning" and order of measure presentation. After selecting the draft battery, feasibility was evaluated in a pilot study prior to the main trial.The battery was feasible to administer and avoided unintended selection bias. Dropout was substantial, however, and differences across sites in baseline assessment completion rates reflected a tendency of a central intake model to function as an initial filter of dropouts, compared with a direct recruitment model.This process holds several potentially useful lessons for investigators.

L’objectif de cet article est d’examiner les relations mere-enfant dans les familles d’enfants presentant un etat limite (EL). Vingt-deux meres ainsi que leur enfant presentant un trouble limite ont ete interroges simultanement a propos de la qualite et du type de leurs interactions. Les profils de perceptions rapportes ont ete compares a ceux de vingt-deux meres et de leur enfant qui ne presentait pas de trouble emotionnel. Des donnees portant, d’une part, sur les perceptions qu’ont les meres de leur style parental ainsi que, d’autre part, sur les perception qu’ont les enfants du style parental de leur mere ont ete recueillies. Les meres d’enfants EL ont dit utiliser plus de controle par la culpabilite et se sont dites plus centrees sur leur enfant que les meres du groupe temoin. Cependant, le fait qu’elles se disent plus centrees sur leur enfant a ete interprete comme etant de la surprotection etant donne la nature des variables composant l’echelle mesurant ce phenomene. Les enfants EL ont rapporte moins d’affection, plus d’agression, plus de negligence et de rejet ainsi que plus de controle de la part de leur mere que les enfants du groupe temoin. Les enfants EL ont rapporte des types d’interactions avec leur mere qui sont caracterises par du controle sans affection. Ces memes types d’interactions ont ete observes chez des adultes EL dans des etudes ulterieures.

Relationship schemas are core elements of personality that guide interpersonal functioning. The aim of this study is to examine stability and change in relationship schemas across two developmental epochs-adolescence and young adulthood-in the stories that people tell about their interactions with others. Using the Core Conflictual Relationship Theme Method, relationship themes were coded from semistructured interviews conducted in adolescence and again at age 25. The sample consisted of 40 participants in a longitudinal study of adolescent and young adult psychological development. There was considerable stability in the frequency with which particular themes were expressed in the narratives of adolescents and young adults. Significant changes from adolescence to young adulthood included a decrease in the perception of others as rejecting and of the self as opposing others. Young adults saw themselves and others more positively, and used a broader repertoire of themes in their relationship narratives than they had as adolescents. The basic continuity and particular changes in relationship schemas found in this study are consistent with knowledge about the adolescent-to-young-adult transition derived from other empirical and clinical findings. Relationship schemas may be rich units of study for learning about the development of interpersonal functioning.

Un protocole de détection de QTL en croisement entre les races Prim'Holstein et Normande a été mené à l'Unité Expérimentale INRA du Pin-au-Haras. Ce programme a pour objectif de détecter et cartographier des QTL responsables de la variabilité intra et entre races. 866 femelles F2 ont été suivies jusqu'en première lactation, ainsi que 324 femelles " F3 " issues d'un père F1 et d'une mère F2. Les phénotypes mesurés concernent les caractères classiquement mesurés en ferme, mais surtout un grand nombre de caractères originaux. Les résultats présentés concernent l'aptitude fromagère des laits individuels, la précocité sexuelle, la reprise de cyclicité post-partum, et la coloration de la robe. Tous les individus F0 à F3 sont génotypés sur la puce bovine 50k d'Illumina. Les détections ont été faites par analyse de liaison et déséquilibre de liaison. L'âge à la puberté est en moyenne de 307 jours (± 51) et son héritabilité est estimée à 0,37. Des QTL sont détectés sur 13 chromosomes (1, 2, 3, 5, 8, 11, 12, 13, 14, 21, 25, 27 et 29), les plus forts étant sur les chromosomes 29 (pic à 26 Mb) et 13 (61 Mb). Le délai de reprise de cyclicité est en moyenne de 31 jours (± 12) et son héritabilité est estimée à 0,17. 14 QTL sont détectés sur 9 chromosomes (1, 3, 5, 8, 11, 17, 21, 26 et 27) avec les plus forts sur les chromosomes 21 (26 Mb) et 26 (33 Mb). Seuls 2 QTL sont communs aux deux caractères, sur le chromosome 21, reflétant leur faible corrélation génétique (0,24). L'aptitude fromagère dépend très fortement du génotype au locus des caséines, ainsi que de la beta-lactoglobuline et de DGAT1. Après prise en compte de ces locus, 5 à 8 QTL sont détectés pour les différents caractères analysés (temps de prise, fermeté du gel, rendement, gras sur sec). Ils sont en général différents entre caractères et ont des effets plus réduits. Concernant le patron de coloration, MC1R est responsable de la couleur, ASIP de la bringeure, MITF de la tête blanche, du pourcentage de blanc, de la couleur des onglons, KIT du pourcentage de blanc et du type de panachure. Une nouvelle région sur le chromosome 8 est mise en évidence et affecte le pourcentage de blanc et le type de panachure.

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The construction of shared meanings in play, pretense enactment, internal state language, and sibling relationship quality were investigated in 40 kindergarteners with an older ( M age=7.10 years) or younger ( M age=3.6 years) sibling. Dyadic strategies to construct shared meanings (e.g., extensions, building on) were positively associated with frequency of pretense and internal state language. Developmental differences indicated that older dyads used more shared meaning strategies, whereas younger dyads engaged in nonmaintenance behaviors (i.e., disruptions to flow of play). Furthermore, firstborn kindergarteners used more nonmaintenance behaviors, whereas second-born kindergarteners extended partner's ideas. Findings highlight the sibling relationship as a context for illuminating social understanding and relationship dynamics during pretend play. [ABSTRACT FROM AUTHOR]

National audience

Des régions du génome portant des mutations récessives délétères ont été détectées dans les trois principales races laitières françaises en recherchant des haplotypes relativement fréquents (>1%) dans la population mais présentant un fort déficit en homozygotes. La détection repose sur l’utilisation des données de typages de la puce BovineSNP50 ® d’Illumina utilisées en sélection génomique (47 878 animaux Holstein, 16 833 Montbéliards, et 11 466 Normands). Trente trois régions incluant les régions déjà décrites associées à Brachyspina, CVM, HH1 et HH3 en race Holstein ont été identifiées. La longueur de ces régions varie de 1 à 4,8 Mb et les fréquences des haplotypes de 1,8 à 9%. Un effet significatif négatif sur la fertilité a été observé pour 10 de ces régions dans les accouplements à risque entre taureaux porteurs et filles de taureaux porteurs, confortant leur association avec des mutations létales à l’état embryonnaire. Des effets significatifs ont également été observés sur la mortinatalité pour 7 haplotypes. Ces régions ont été ensuite analysées avec des données de séquence complète du génome de taureaux porteurs et contrôle (45 animaux au total). Des mutations candidates très fortes ont été mises en évidence, dont trois déjà connues dans les gènes FANCI (Brachyspina), SLC35A3 (CVM), et APAF1 (HH1) et quatre nouvelles mutations avec des effets prédits très délétères sur la structure protéique dans les gènes GART, SMC2, SLC37A2, et NOA1. En conclusion, cette étude montre un aspect jusqu’à présent inconnu de la consanguinité dans les races bovines sélectionnées. Alors qu’une éradication systématique serait extrêmement coûteuse financièrement pour les programmes de sélection, une contre-sélection doit être entreprise pour diminuer progressivement la fréquence de ces mutations. Les plans d’accouplement doivent dès à présent éviter les accouplements à risque., Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina BovineSNP50 ® Beadchip haplotypic data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-three candidate haplotypes were identified including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in the Holstein breed. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.8 up to 9%. A significant negative effect on calving rate was observed for 10 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Significant effects were also detected on stillbirth for 7 haplotypes. These regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Seven strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and four novel mutations with very damaging predicted effect on the protein structure were detected in GART, SMC2, SLC37A2, and NOA1 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Whereas a systematic eradication would be extremely costly and damaging for the breeding scheme, a gradual counter selection must be undertaken to decrease their frequency and an appropriate mating plan must be carried out to avoid matings at risk.

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International audience

International audience; La lipolyse spontanée (LS) du lait dépend de nombreux facteurs d’élevage, dont la fréquence de traite, et la génétique de l’animal. Nous avons donc testé l’effet du gène DGAT1, polymorphique au locus K232A, sur la LS dans un contexte de variation de la fréquence de traite. Huit vaches « KK », 8 vaches « KA » et 5 vaches « AA » ont été utilisées. L’essai s’est déroulé sur 3 périodes successives : une semaine de référence en bitraite, 3 semaines de monotraite et une semaine de bitraite. Les prélèvements ont été effectués à J-4, J0 (date de passage en monotraite), J1, J2, J7 et J24, pour évaluer le taux butyreux (TB), le taux protéique (TP), la composition en acides gras (AG) et en protéines, et la LS. Les vaches « KK » ont présenté un TB et un TP plus élevés, une production laitière plus faible, un pourcentage de caséines ? plus élevé que les vaches « AA ». Les profils en AG n’ont pas présenté de différence. En bitraite, la LS a été deux fois plus élevée chez les vaches « KK » que chez les vaches « KA » et « AA » (1,28 vs 0,59 et 0,63 mEq/100g de MG respectivement, pendant la période de référence).En monotraite, la LS a été identique dans les 3 groupes et inférieure à 0,2 mEq/100 g de MG. L’existence d’un déterminisme génétique de la lipolyse, confirmée par une étude à plus grande échelle, pourrait être prise en compte lors de la sélection génétique des animaux.