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Alzheimer's disease (AD) is the most common form of dementia and is characterized by progressive memory loss and cognitive decline, affecting behavior, speech, and motor abilities. The neuropathology of AD includes the formation of extracellular amyloid-β plaque and intracellular neurofibrillary tangles of phosphorylated tau, along with neuronal loss. While neuronal loss is an AD hallmark, cell-cell communication between neuronal and non-neuronal cell populations maintains neuronal health and brain homeostasis. To study changes in cellcell communication during disease progression, we performed snRNA-sequencing of the hippocampus from female 3xTg-AD and wild-type littermates at 6 and 12 months. We inferred differential cell-cell communication between 3xTg-AD and wild-type mice across time points and between senders (astrocytes, microglia, oligodendrocytes, and OPCs) and receivers (excitatory and inhibitory neurons) of interest. We also assessed the downstream effects of altered glia-neuron communication using pseudobulk differential gene expression, functional enrichment, and gene regulatory analyses. We found that glia-neuron communication is increasingly dysregulated in 12-month 3xTg-AD mice. We also identified 23 AD-associated ligand-receptor pairs that are upregulated in the 12-month-old 3xTg-AD hippocampus. Our results suggest increased AD association of interactions originating from microglia. Signaling mediators were not significantly differentially expressed but showed altered gene regulation and TF activity. Our findings indicate that altered glia-neuron communication is increasingly dysregulated and affects the gene regulatory mechanisms in neurons of 12-month-old 3xTg-AD mice., Competing Interests: Conflict of interest disclosure: The authors declare that they do not have competing interests.

Bacteria use the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) to control biofilm formation and other key phenotypes in response to environmental signals. Changes in oxygen levels can alter c-di-GMP signaling through a family of proteins termed globin coupled sensors (GCS) that contain diguanylate cyclase domains. Previous studies have found that GCS diguanylate cyclase activity is controlled by ligand binding to the heme within the globin domain, with oxygen binding resulting in the greatest increase in catalytic activity. Herein, we present evidence that heme-edge residues control O 2 -dependent signaling in PccGCS, a GCS protein from Pectobacterium carotovorum, by modulating heme distortion. Using enzyme kinetics, resonance Raman spectroscopy, small angle X-ray scattering, and multi-wavelength analytical ultracentrifugation, we have developed an integrated model of the full-length PccGCS tetramer and have identified conformational changes associated with ligand binding, heme conformation, and cyclase activity. Taken together, these studies provide new insights into the mechanism by which O 2 binding modulates activity of diguanylate cyclase-containing GCS proteins., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Emily Weinert reports financial support was provided by National Science Foundation. Emily Weinert reports financial support was provided by Herman Frasch Foundation for Chemical Research. Yilin Liu reports financial support was provided by National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Skeletal muscle has recently arisen as a regulator of central nervous system (CNS) function and aging, secreting bioactive molecules known as myokines with metabolism-modifying functions in targeted tissues, including the CNS. Here, we report the generation of a transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of transcription factor E-B (TFEB). We discovered that the resulting geroprotective effects in skeletal muscle reduce neuroinflammation and the accumulation of tau-associated pathological hallmarks in a mouse model of tauopathy. Muscle-specific TFEB overexpression significantly ameliorates proteotoxicity, reduces neuroinflammation, and promotes transcriptional remodeling of the aged CNS, preserving cognition and memory in aged mice. Our results implicate the maintenance of skeletal muscle function throughout aging in direct regulation of CNS health and disease and suggest that skeletal muscle originating factors may act as therapeutic targets against age-associated neurodegenerative disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A spectrophotometric method to measure hydrolysis of the bacterial second messenger cyclic dimeric guanosine monophosphate is described for characterization of enzymes under aerobic and anaerobic conditions. The method allows for obtaining all necessary data to calculate K M and k cat from reactions within a single 96-well plate that can be measured using a standard plate reader. The spectrophotometric assay has been used to measure the rates and obtain Michaelis-Menten parameters for the c-di-GMP phosphodiesterase DcpG with the sensor domain in various ligation states., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Bifunctional enzymes, which contain two domains with opposing enzymatic activities, are widely distributed in bacteria, but the regulatory mechanism(s) that prevent futile cycling are still poorly understood. The recently described bifunctional enzyme, DcpG, exhibits unusual heme properties and is surprisingly able to differentially regulate its two cyclic dimeric guanosine monophosphate (c-di-GMP) metabolic domains in response to heme gaseous ligands. Mutagenesis of heme-edge residues was used to probe the heme pocket and resulted in decreased O 2 dissociation kinetics, identifying roles for these residues in modulating DcpG gas sensing. In addition, the resonance Raman spectra of the DcpG wild type and heme-edge mutants revealed that the mutations alter the heme electrostatic environment, vinyl group conformations, and spin state population. Using small-angle X-ray scattering and negative stain electron microscopy, the heme-edge mutations were demonstrated to cause changes to the protein conformation, which resulted in altered signaling transduction and enzyme kinetics. These findings provide insights into molecular interactions that regulate DcpG gas sensing as well as mechanisms that have evolved to control multidomain bacterial signaling proteins.

Cyclic dimeric guanosine monophosphate (c-di-GMP) serves as a second messenger that modulates bacterial cellular processes, including biofilm formation. While proteins containing both c-di-GMP synthesizing (GGDEF) and c-di-GMP hydrolyzing (EAL) domains are widely predicted in bacterial genomes, it is poorly understood how domains with opposing enzymatic activity are regulated within a single polypeptide. Herein, we report the characterization of a globin-coupled sensor protein (GCS) from Paenibacillus dendritiformis (DcpG) with bifunctional c-di-GMP enzymatic activity. DcpG contains a regulatory sensor globin domain linked to diguanylate cyclase (GGDEF) and phosphodiesterase (EAL) domains that are differentially regulated by gas binding to the heme; GGDEF domain activity is activated by the Fe(II)-NO state of the globin domain, while EAL domain activity is activated by the Fe(II)-O 2 state. The in vitro activity of DcpG is mimicked in vivo by the biofilm formation of P. dendritiformis in response to gaseous environment, with nitric oxide conditions leading to the greatest amount of biofilm formation. The ability of DcpG to differentially control GGDEF and EAL domain activity in response to ligand binding is likely due to the unusual properties of the globin domain, including rapid ligand dissociation rates and high midpoint potentials. Using structural information from small-angle X-ray scattering and negative stain electron microscopy studies, we developed a structural model of DcpG, providing information about the regulatory mechanism. These studies provide information about full-length GCS protein architecture and insight into the mechanism by which a single regulatory domain can selectively control output domains with opposing enzymatic activities., Competing Interests: The authors declare no competing interest.

Objectives: To characterize the literature on operative interventions for proximal humerus nonunions in adults. Second, to identify prognostic factors associated with outcomes for locked plate open reduction and internal fixation (ORIF)., Data Sources: PubMed, EMBASE, MEDLINE, Scopus, and Cochrane databases were searched for articles from 1990 to 2020., Study Selection: Studies reporting outcomes of proximal humerus nonunions managed with ORIF, hemiarthroplasty (HA), total shoulder arthroplasty (TSA), or reverse TSA (RTSA) were included. Studies failing to stratify outcomes by treatment or fracture sequelae were excluded., Data Extraction: Two authors independently extracted data and appraised study quality using MINORS score., Data Synthesis: Descriptive statistics were reported. Outcomes for ORIF and arthroplasty groups were not compared due to differing patient populations., Conclusions: Thirty-seven articles were included, representing 508 patients (246 ORIF, 137 HA/TSA, and 125 RTSA). Patients managed by ORIF were younger with simpler fracture patterns than those managed by arthroplasty. Regarding ORIF, locked plates achieved highest union rates (97.0%), but clinical outcomes were comparable with all plate fixation constructs [forward flexion (FF): 123-144°; external rotation: 42-46°; Constant score: 75-84]. Complication and reoperation rates for ORIF were 26.0% and 14.6%, respectively. Furthermore, subgroup analysis of locked plate ORIF demonstrated shorter consolidation time with initial conservative fracture management (4.3 vs. 6.0 months) and autograft use (3.9 vs. 5.5 months). With arthroplasty, RTSA demonstrated greater forward flexion (109.4° vs. 97.2°) but less external rotation (16.5° vs. 36.8°) than HA/TSA. Complication and reoperation rates were 18.2% and 10.9% for HA/TSA and 21.6% and 14.4% for RTSA, respectively., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Aims: Heterotopic ossification (HO) is a potentially devastating complication of the surgical treatment of a proximal humeral fracture. The literature on the rate and risk factors for the development of HO under these circumstances is lacking. The aim of this study was to determine the incidence and risk factors for the development of HO in these patients., Methods: A retrospective analysis of 170 patients who underwent operative treatment for a proximal humeral fracture between 2005 and 2016, in a single institution, was undertaken. The mean follow-up was 18.2 months (1.5 to 140). The presence of HO was identified on follow-up radiographs., Results: The incidence of HO was 15% (n = 26). Our multivariate model revealed that male sex (odds ratio (OR) 3.57, 95% confidence interval (CI) 1.30 to 9.80 compared to female) and dislocation as the initial injury (OR 5.01, 95% CI 1.31 to 19.22) were significantly associated with the formation of HO (p < 0.05) while no significant associations were seen for the age of the patient, the characteristics of the injury, or the type of operative treatment., Conclusion: This retrospective radiological study is the first to investigate the association between the method of surgical treatment for a proximal humeral fracture and the formation of HO postoperatively. We found that male sex and dislocation as the initial injury were risk factors for HO formation, whereas the method of surgical treatment, the age of the patient, and the pattern of the fracture were not predictive of HO formation. While additional studies are needed, these findings can help to identify those at an increased risk for HO formation under these circumstances. Cite this article: Bone Joint J 2020;102-B(4):539-544.

Background: Severe glenohumeral arthritis in the young/active patient remains challenging. Historically, glenohumeral arthrodesis was recommended with limited return of function. Total shoulder arthroplasty has shown increasing survivorship at 15 years; however it is still not ideal for young patients. Biologic resurfacing of the glenoid with humeral head replacement has shown promising results., Methods: The PubMed and Embase databases were queried for studies evaluating outcomes of glenoid biologic resurfacing with autograft or allograft. Two independent reviewers performed a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines., Results: Eleven studies (268 shoulders, 264 patients) were included. Minimum follow-up was 24 months in all but one study; patient age ranged from 14 to 75 years. Glenoid grafts used included 44.3% lateral meniscus allografts, 25.4% human acellular dermal matrix, 14.2% Achilles tendon allografts, 11.6% shoulder joint capsules, and 4.5% fascia lata autografts. Studies reported significantly improved American Shoulder and Elbow Surgeons, Visual Analog Scale, and Simple Shoulder Test scores postoperatively; 43.3% were failures (Neer's evaluation of unsatisfactory or requiring revision). Infection occurred in 12/235., Conclusions: Biologic resurfacing of the glenoid with a metallic humeral component can provide a significant improvement in pain, motion, and standardized outcomes scores in the well-indicated situation. Appropriate counseling is required with an appreciated complication rate of over 36% and a revision rate of 34%., (© 2019 The British Elbow & Shoulder Society.)

Introduction: Tranexamic acid (TXA) is increasingly used to reduce blood loss in lower extremity arthroplasty, but limited data exist for its effectiveness in patients undergoing shoulder arthroplasty. We aimed to use national data to assess the frequency of use and effectiveness of TXA in patients undergoing shoulder arthroplasty., Methods: Using national claims data from patients undergoing shoulder arthroplasty (Premier Healthcare; 2010 to 2016; n = 82,512; 429 hospitals), we categorized patients according to whether they received perioperative TXA. Multilevel multivariable regression models measured associations between TXA and blood transfusion risk, combined complications (including thromboembolic events, acute renal failure, cerebral infarction, and acute myocardial infarction), and length and cost of hospitalization. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported., Results: Overall, TXA was used in 12.8% (n = 10,582) of patients with a strong increasing trend. After adjustment for relevant covariates, TXA use (compared with no TXA use) was associated with a 36% decrease in transfusion risk (OR, 0.64; 95% CI, 0.52 to 0.77; P < 0.05) and a 35% decreased risk for combined complications (OR, 0.65; 95% CI, 0.50 to 0.83; P < 0.05). Moreover, TXA use was associated with 6.2% shorter hospital stay (95% CI, -8.0% to -4.4%; P < 0.05), whereas no difference was observed with the cost of hospitalization., Conclusion: In this first large-scale study assessing TXA use and effectiveness in patients undergoing shoulder arthroplasty, we found that although TXA utilization is still low, it is associated with a marked decrease in transfusion risk with no increases in complication risk. Effects on the length and cost of hospitalization appeared minor. Future studies should assess whether higher volumes of TXA utilization would translate into more gains on the length and cost of hospitalization., Level of Evidence: Level III.

Introduction: Medical vocabulary that conveys different meanings to different groups of readers can lead to confusion and potential misinterpretation of diagnoses. This article reviews words used by radiologists that convey information to the orthopedic surgeon and patient that is different from what the radiologist intended. These terms include meniscal tears, ligament sprains, partial tendon tears, bone bruises, bone contusions, articular cartilage injury, disc bulges, disc herniations, and joint subluxation. These words can, for example, suggest a traumatic etiology when in fact the condition is atraumatic, and they can imply a surgical treatment where none is indicated. This problem is further magnified in the arena of personal injury litigation., Materials and Methods: The terms tear, bruise, contusion, injury, sprain, bulge, herniation, and subluxation are defined and analyzed for their ambiguous use, i.e., their actual versus intended meaning or other interpretation., Results: Abnormalities and variations observed on musculoskeletal magnetic resonance (MR) images are often multi-factorial and may not be the source of any given patient's symptoms. The same MR image findings can have a congenital, traumatic, or degenerative source., Conclusions: Radiology vocabulary that invokes a singular traumatic event as a cause of an MRI finding can significantly mislead patients (as well as judges and juries). We propose that some terms be either avoided entirely when the findings are of uncertain etiology. At the very least, the various meanings of the terms need to be spelled out. Greater cooperation between orthopedic surgeons and radiologists on this matter would be beneficial to patient care.

Background: Following a case of medial meniscal repair via an inside-out repair, a patient developed acute postoperative electric shock-like paresthesias of the proximal medial calf with any knee flexion beyond 80°. Open saphenous nerve exploration revealed entrapment by suture material of an unnamed branch off the sartorial branch of the saphenous nerve. Symptoms resolved immediately with release. The objective of the study was to perform a cadaveric study to examine the existence and frequency of these previously under-reported branches of the sartorial branch of the saphenous nerve., Methods: In 16 knees from eight fresh, matched whole cadavers, the medial structures of the knee were exposed, reproducible anatomical structures were identified, and previously under-described posteromedial branches of the sartorial nerve were identified and measured in relation to surrounding structures and the joint line., Results: The saphenous nerve, its sartorial and infrapatellar branches, and its posteromedial branches were identified in all specimens. The sartorial nerve divided from the saphenous nerve an average of 4.8 cm proximal to the medial femoral epicondyle. Between one and four further posteromedial branches off the sartorial nerve were identified. These branches formed at a range of 5.3 cm proximal to 3.0 cm distal to the joint line., Conclusions: This cadaveric study establishes the consistent presence of a posteromedial branch off the sartorial nerve. It was consistently located near the posteromedial joint line. These branches are at risk for injury during medial meniscus repairs due to entrapment by suture materials, or during other surgical procedures near the posteromedial aspect of the knee., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Reverse total shoulder arthroplasty (RSA) accounts for nearly one-third of shoulder arthroplasty utilization nationally. The complication rate has increased concurrently. Consensus is lacking regarding the incidence, etiology, and treatment of acromial or scapular spine fractures after RSA. The purpose of our study was to perform a systematic review of the literature to analyze the occurrence and outcomes of this complication., Methods: The MEDLINE, Embase, Google Scholar, and Cochrane databases were queried in late 2017 for combinations of the words "acromial," "fracture," "reverse," "shoulder," and "arthroplasty." We included all studies that contained a clearly defined performance of RSA, acromial fracture(s) noted, and treatment (if any) and outcomes of treatment. The initial search yielded 50 studies; 32 met the inclusion criteria., Results: Among 3838 RSAs, 159 acromial fractures were reported, for an overall incidence of 4.14%; the mean time to diagnosis from surgery was 9 months (range, 1.3-24 months). Treatments included nonoperative treatment in a sling or abduction brace in 139 cases and open reduction-internal fixation in 20. Regardless of treatment, patients reported inferior function after fracture compared with initially after RSA. Forward flexion was 95° (range, 30°-110°), abduction was 76° (range, 30°-180°), the Constant score was 63 (range, 59-67.5), and the American Shoulder and Elbow Surgeons score was 57 (range, 7-83); all values were reduced compared with patients without fractures., Conclusion: This study suggests the occurrence of acromial fractures after RSA is a common event, with a rate of over 4%. These fractures correlate with worse postoperative outcomes regardless of treatment method; open reduction-internal fixation was not shown to be clinically superior despite a limited complication rate. Additional high-quality studies addressing acromial spine fracture after RSA are needed., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Intravenous acetaminophen (IV APAP) is an option in multimodal postoperative analgesia. Prior trials focus on hip and knee arthroplasties, whereas large-scale data on utilization and effectiveness in shoulder arthroplasties are lacking., Methods: Data on 67,494 (452 hospitals) partial/total shoulder arthroplasties were extracted from the Premier claims database (2011-2016). Patients were categorized by receipt and dosage of IV APAP. Multilevel models measured associations between IV APAP and opioid utilization (in oral morphine equivalents), length/cost of stay and opioid-related complications. Effect estimates (adjusted % change) with 95% confidence intervals (CIs) are reported., Results: IV APAP was used in 17.7% (n = 11,949) of patients with an increasing utilization trend. Most patients received only one dose on the day of surgery (69.5%; n = 8308). When adjusting for relevant covariates, IV APAP was not associated with meaningful effects on outcomes. Specifically, its use (versus no use) was not associated with decreased (but rather somewhat increased) opioid utilization: + 5.4% (CI 3.6-7.1%; P < 0.05)., Conclusion: In this first large-scale study that assesses IV APAP in shoulder arthroplasties, IV APAP use was not associated with decreased opioid utilization or the length/cost of stay. These results do not support routine use of IV APAP in this cohort, especially given its high cost., The Translational Potential for This Article: Multimodal pain control to assist in reducing the opioid pain medications are seen as a route to improved postoperative patient outcomes, better pain control and expedited hospital discharge. Acetaminophen plays a significant role in these protocols in many institutions, but it is not established if this expensive IV formulation is superior to the oral formulation. This study evaluates the use and effectiveness of IV acetaminophen following shoulder arthroplasty at a large number of institutions.

Background: Biceps tenodesis reduces the incidence of Popeye deformity occurring with tenotomy, but pain may occur with tenodesis superior to or within the bicipital groove. Arthroscopic suprapectoral tenodesis is an attractive alternative. The purpose of this study was to establish landmarks for arthroscopic suprapectoral tenodesis and determine the appropriate fixation point to optimize muscle tension., Methods: Twelve fresh cadaveric shoulders were dissected. Urethane polymer was injected into the axillary artery. The position of the anterior branch of the axillary nerve was marked. The transverse humeral ligament was split, exposing the biceps (long head of the biceps [LHB]) from its origin to the pectoralis major tendon (PMT). The intra-articular portion was released. Measurements were taken from the proximal tendon to described landmarks., Results: The mean length of the intra-articular LHB was 2.53 cm (range, 1.72-3.55 cm). The mean distance from the LHB origin to the inferior lesser tuberosity (LT) was 5.58 cm (range, 4.02-6.87 cm), and that to the superior border of the PMT was 8.46 cm (range, 6.46-10.78 cm). The suprapectoral tenodesis zone (inferior LT to superior PMT) was 2.96 cm (range, 1.54-4.40 cm). In all specimens, a branch of the anterior humeral circumflex arose medial to the LHB and distal to the LT and crossed the suprapectoral zone from medial to lateral at 1.49 ± 0.42 cm proximal to the PMT, approximately at the level of the axillary nerve. The musculocutaneous nerve was on average 3.06 cm (range, 1.86-3.76 cm) from the tenodesis zone., Conclusion: A branch of the anterior humeral circumflex is a reliable landmark for identifying the mid-suprapectoral zone. The distance from the proximal LHB tendon to this crossing vessel averaged 6.32 cm in female specimens and 8.28 cm in male specimens. These findings allow appropriate tensioning of the LHB during arthroscopic suprapectoral tenodesis., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Faced with a patient who presents with unexplained disproportionate pain, a surgeon may be tempted to diagnose a low pain threshold, malingering, poor coping, anxiety, or other emotional condition. However, a variety of conditions must be ruled out before the orthopedist can prescribe watchful waiting. Computed tomography and magnetic resonance imaging can detect occult fractures, acute spinal conditions or vascular occlusions, but early on are inadequate to diagnose a compartment syndrome, necrotizing fasciitis, or reflex sympathetic dystrophy (RSD). These diagnoses underpin a pain-out-of-proportion situation whereby the patient presents with disproportionate pain following a sometimes minor trauma with normal imaging studies and otherwise nonspecific presentations. Though these conditions are well described in the literature, investigations of malpractice data reveal a non-negligible prevalence of missed diagnoses for each of these entities. Determining that a patient exhibits otherwise unexplained pain-out-of-proportion situation is the first step in making a timely diagnosis.

Debate remains about the appropriate treatment of the asymptomatic side following treatment of a unilateral slipped capital femoral epiphysis (SCFE). A 12-year-old boy with a seizure disorder presented with an unstable SCFE on the left hip following a seizure. He underwent percutaneous pinning of the left only. At 8 months postoperatively, he returned with an unstable slip of the right hip, again following a seizure. No literature discussing the treatment of patients with risk of SCFE and seizure disorders was identified. Further study may identify an increased incidence of contralateral slip following an initial slip in this population. If a greater risk exists, contralateral prophylactic fixation at time of index surgery may be indicated.

Background: As the prevalence of total hip arthroplasty (THA) expands, so too will complications and patient dissatisfaction. The goal of this study was to identify the common etiologies of malpractice suits and costs of claims after primary and revision THAs., Methods: Analysis of 115 malpractice claims filed for alleged neglectful primary and revision THA surgeries by orthopedic surgeons insured by a large New York state malpractice carrier between 1983 and 2011., Results: The incidence of malpractice claims filed for negligent THA procedures is only 0.15% per year in our population. In primary cases, nerve injury ("foot drop") was the most frequent allegation with 27 claims. Negligent surgery causing dislocation was alleged in 18 and leg length discrepancy in 14. Medical complications were also reported, including 3 thromboembolic events and 6 deaths. In revision cases, dislocation and infection were the most common source of suits. The average indemnity payment was $386,153 and the largest single settlement was $4.1 million for an arterial injury resulting in amputation after a primary hip replacement. The average litigation cost to the insurer was $61,833., Conclusion: Nerve injury, dislocation, and leg length discrepancy are the most common reason for malpractice after primary THA. Orthopedic surgeons should continue to focus on minimizing the occurrence of these complications while adequately incorporating details about the risks and limitations of surgery into their preoperative education., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: As the number of total knee arthroplasties (TKAs) increases, the number of associated complications will also increase. Our goal with this study was to identify common causes of and financial trends relating to malpractice claims filed after TKA., Methods: We analyzed malpractice claims filed for alleged neglectful primary and revision TKA surgeries performed between 1982 and 2012 by orthopaedic surgeons insured by a large New York state malpractice carrier., Results: We identified 69 primary and 8 revision TKAs in the malpractice carrier's database. All cases were performed between 1982 and 2012; all claims were closed between 1989-2015. The most frequent factor leading to lawsuits for primary TKA was chronic pain or dissatisfaction in 12 cases, followed by nerve palsy in 8, postoperative in-hospital falls in 5, and deep vein thrombosis or pulmonary embolism in 3. Medical complications included acute respiratory distress syndrome, cardiac arrest, and decubitus ulcers. Contracture was most common after revision TKA (three of eight cases). Mean indemnity was $325,369, and the largest single settlement was $2.42 million. The average expense relating to the defense of these cases was $66,365., Conclusions: Orthopaedic surgeons should continue to focus attention on prevention of complications and on preoperative patient education. Preoperative counseling regarding the risks of incomplete pain relief could reduce substantially the number of suits relating to primary TKAs.

Study Design: Systematic literature review and meta-analysis of studies published in English language., Objective: Return to play after anterior cervical discectomy and fusion (ACDF) in contact athletes remains a controversial topic with no consensus opinion in the literature. Additional information is needed to properly advise and treat this population of patients. This study is a meta-analysis assessing return to competitive contact sports after undergoing an ACDF., Methods: A literature search of Medline, Embase, and Cochrane Reviews was performed to identify investigations reporting return to play following ACDF in professional contact athletes. The pooled results were performed by calculating the effect size based on the logic event rate. Studies were weighted by the inverse of the variance, which included both within and between-study error. Confidence intervals (CIs) were reported at 95%. Heterogeneity was assessed using the Q statistic and I 2 . Sensitivity analysis and publication bias calculations were performed., Results: The initial literature search resulted in 166 articles, of which 5 were determined relevant. Overall, return to play data was provided for 48 patients. The pooled clinical success rate for return to play was 73.5% (CI = 56.7%, 85.8%). The logit event rate was calculated to be 1.036 (CI = 0.270, 1.802), which was statistically significant ( P = .008). The studies included in this meta-analysis demonstrated minimal heterogeneity with Q value of 4.038 and I 2 value of 0.956., Conclusions: Elite contact athletes return to competition 73.5% of the time after undergoing ACDF. As this is the first study to pool results from existing studies, it provides strong evidence to guide decision making and expectations in this patient population., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Prior database studies have shown that complication rates following surgical treatment of proximal humerus fractures are low. However, diabetes has been shown across orthopedics to have significantly increased risks of postoperative complications. The purpose of our study was to identify complications for which diabetic patients are at increased risk following operative treatment of proximal humerus fractures., Methods: The National Surgical Quality Improvement Program database from 2005 to 2014 identified patients >18 years undergoing open reduction-internal fixation for proximal humerus fractures. Patients with incomplete perioperative data were excluded. Patients with non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) were compared with nondiabetic patients using multivariate logistic regression analysis. Odds ratio (OR) was calculated with a 95% confidence interval, and the significance level was held at P  < .05., Results: There were 1391 patients identified; 1147 (82%) were not diabetic, 91 (7%) had IDDM, and 153 (11%) had NIDDM. Of these, 39.68% (550) were obese (body mass index >30.0). Hypertension, dyspnea, and chronic obstructive pulmonary disease were the most frequent concurrent patient factors in diabetic patients. Postoperatively, patients with diabetes had a statistically significant higher risk of pneumonia (OR, 217.80; P  = .002) and length of stay >4 days (OR, 2.05; P  = .010). Among diabetics, non-insulin-dependent diabetics had a greater risk of sepsis (OR, 25.84; P  = .022) and pneumonia (OR, 12.19; P  = .013) than insulin-dependent diabetics., Conclusion: Both NIDDM and IDDM were associated with a number of adverse postoperative events. Importantly, NIDDM was found to be an independent risk factor for postoperative sepsis and pneumonia, whereas IDDM was identified as an independent risk factor for pneumonia and prolonged length of stay (≥4 days).

Study Design  Observational study. Objective  Studies have shown a correlation between obesity and lumbar spine pathology, but also that obese patients have higher rates of complication following lumbar spine surgery. It is unknown if obese patients have clinical gains following lumbar spine surgery comparable to the gain of normal-weight patients. This study investigated the correlation of obesity and the delta change in outcomes in a single surgeon's cohort of normal-weight and obese patients undergoing minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF). Methods  A retrospective review was performed of a single surgeon's patients at an academic medical center who underwent MIS TLIF between July 2011 and December 2013. Statistical analyses included independent sample t test for continuous variables, Fisher exact test for categorical data, and repeated measures two-way analysis of variance to assess the interaction between obesity status and the change in Short-Form Health Survey 12 (SF-12) results. Results  Thirty-eight patients from a single institution were reviewed, and 19 had a body mass index greater than 30. The nonobese and obese postoperative SF-12 mental composite scores (MCS; 52.70 ± 2.50 versus 52.16 ± 1.91; p  = 0.87) and physical composite scores (PCS; 45.56 ± 2.72 versus 41.03 ± 2.65; p  = 0.24) did not show any significant differences. There was no significant interaction between obesity and change in SF-12 MCS ( F [1, 36] = 0.96, p  = 0.33) or SF-12 PCS ( F [1, 36] = 0.74, p  = 0.40) between the pre- and postoperative scores. There was a significant effect of obesity on SF-12 PCS scores ( F [1, 36] = 7.15, p  = 0.01). Conclusions  Patients undergoing MIS TLIF sustain meaningful and significant gains in SF-12 MCS and PCS that is not impacted by their obesity status.

The synthesis of 1,2-oxaborines is accomplished via the reaction of pentaarylboroles with N-methylmorpholine-N-oxide via a 1,1-insertion reaction. The aromatic nature of 1,2-oxaborines was evaluated by computing nuclear independent chemical shift (NICS) values. Collectively, the experimental and computational studies indicate the unsaturated central BOC4 ring has appreciable aromatic character.

Purpose: To determine factors associated with grade IV cartilage defects in the hip in patients undergoing hip arthroscopy with joint pain., Methods: Data from consecutive patients who underwent hip arthroscopy performed by a single surgeon over a period of 4 years were included in this study. The study group included 1,097 patients (491 women and 606 men; mean age, 37 years) who underwent hip arthroscopy for pain, had no prior hip surgery, and were aged 18 years or older. Preoperative radiographs, patient demographic characteristics, and operative details were used to identify risk factors for cartilage defects., Results: Grade IV chondral defects were present in 308 of 1,097 hips (28%). Isolated chondral lesions were more frequently observed on the acetabulum (76%) than on the femoral head (24%). Defects of the acetabulum were more commonly anterosuperior (94.7%) and less commonly posterolateral (5.3%). Patients with less than 2 mm of joint space on preoperative radiographs were 8 times more likely to have a grade IV lesion than those with more than 2 mm. Men were more likely than women to have grade IV lesions (35% v 19%, P = .0001); patients with grade IV lesions were older than those without (42 years v 34 years, P = .0001). Hips with grade IV lesions had significantly higher alpha angles than those without (74° v 70°, P = .0001). Patients with grade IV defects reported a longer duration of symptoms than those without (37 months v 27 months, P = .007). Independent risk factors for the presence of grade IV chondral defects were less than 2 mm of joint space, male gender, increasing age, larger alpha angle, and longer duration of symptoms., Conclusions: Grade IV chondral defects in patients undergoing hip arthroscopy were associated with decreased joint space, increased time from symptom onset to arthroscopy, male gender, and larger alpha angles associated with femoroacetabular impingement., Level of Evidence: Level IV, prognostic case series., (Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Study Design: Systematic literature review and meta-analysis of English language studies., Objective: This study is a meta-analysis assessing elite athlete's return-to-play (RTP) rates after a lumbar herniated nucleus pulposus (HNP) treated with microdiscectomy. Additionally, we compare RTP rates of those treated operatively versus nonoperatively., Summary of Background Data: Microdiscectomy for a lumbar HNP in elite athletes remains a controversial subject with no consensus in the literature regarding true RTP., Methods: A literature search of Medline, Embase, and Cochrane Reviews was performed. The pooled results were analyzed by calculating the effect size based on the logit event rate. Studies were weighted by the inverse of the variance, which included both within and between study errors. Confidence intervals (CIs) were reported at 95%. Heterogeneity was assessed using the Q statistic and I., Results: The initial literature search resulted in 547 articles, of which 14 were determined relevant on abstract review. Overall, nine studies provided data for 558 patients who underwent a lumbar microdiscectomy. The pooled clinical success rate was 83.5% (CI: 79.7%, 88.0%), which was statistically significant (P < 0.0001). The studies demonstrated minimal heterogeneity Q value of 7.41 and I value of 5.53. Four studies included operative and nonoperative cohorts. The odds ratio of RTP with a symptomatic lumbar disc herniation was 1.13 (CI: 0.37-5.90). There was no statistical difference in RTP between the two groups (P = 0.59)., Conclusion: Elite athletes return to competition 83.5% of the time after undergoing a single level lumbar microdiscectomy. Additionally, when comparing lumbar microdiscectomy to non-operative treatment, there is no difference in RTP rates, suggesting that a more aggressive approach to managing a symptomatic HNP in this population with earlier surgical intervention may be employed judiciously if timing necessitates for the athlete's benefit., Level of Evidence: 3.

The objective of this study was to compare calving traits, BCS, milk production, fertility, and survival of Holstein-Friesian (HF) and Norwegian Red (NR) dairy cattle in moderate-concentrate input systems. The experiment was conducted on 19 commercial Northern Ireland dairy farms, and involved 221 HF cows and 221 NR cows. Cows completed 5 lactations during the experiment, unless they died or were culled or sold. Norwegian Red cows had a lower calving difficulty score than HF cows when calving for the first and second time, but not for the third and fourth time. At first calving, the incidence of stillbirths for NR cows was 4%, compared with 13% for HF cows, whereas no difference existed between breeds in the proportion of calves born alive when calving for the second time. When calving for the first time, NR cows had a poorer milking temperament than HF cows, whereas milking temperament was unaffected by breed following the second calving. Holstein-Friesian cows had a higher full-lactation milk yield than NR cows, whereas NR cows produced milk with a higher milk fat and protein content. Full-lactation fat + protein yield was unaffected by genotype. Norwegian Red cows had a lower somatic cell score than HF cows during all lactations. Although NR cattle had a higher BCS than the HF cows during lactations 1 and 2, no evidence existed that the 2 genotypes either lost or gained body condition at different rates. Conception rates to first artificial insemination were higher with the NR cows during lactations 1 to 4 (57.8 vs. 40.9%, respectively), with 28.5% of HF cows and 11.8% of NR cows culled as infertile before lactation 6. A greater percentage of NR cows calved for a sixth time compared with HF cows (27.2 vs. 16.3%, respectively). In general, NR cows outperformed HF cows in traits that have been historically included in the NR breeding program., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: All patients considering joint-preserving hip arthroscopy should be educated on the risk of THA after arthroscopy. The degree of radiographic osteoarthritis predicts subsequent THA. To provide patients with the best information, the best radiographic measure that predicts THA after hip arthroscopy should be identified., Questions/purposes: We therefore determined if Tönnis grade, Kellgren-Lawrence grade, or joint space narrowing was superior in predicting THA after hip arthroscopy., Methods: We retrospectively reviewed 203 patients 50 years of age or older treated with hip arthroscopy between March 2007 and October 2010. Of these, 96 patients met the study inclusion criteria. Sixty-five did not undergo THAs during the followup time (non-THA group) and 31 patients did (THA group). We determined Tönnis grade, Kellgren-Lawrence grade, and/or joint space narrowing before arthroscopy. The median followup for the non-THA group was 54 months (95% confidence interval, 49.9-58.9 months)., Results: In 81% of the patients, joint space accurately predicted THA or non-THA, whereas Kellgren-Lawrence was accurate in 73% and Tönnis grade was accurate in 65%. On binary logistic regression, the only predictor (r(2) = 0.45) of THA was joint space of 2 mm or less., Conclusions: Measuring joint space by determining if any measurement is 2 mm or less predicts patients progressing to THA after hip arthroscopy approximately 80% of the time. At this early time point, joint space measurements were the most accurate predictor of THA and should be used in patient education to define the risk of early failure from hip arthroscopy.

Femoroacetabular impingement (FAI) is widely understood to be an underlying etiology of injuries to the acetabular labrum and cartilage in the adult hip, although somewhat less attention has previously been spent on its incidence in the pediatric and adolescent populations. Initially recognized as a consequence of periacetabular osteotomies performed for developmental dysplasia of the hip, it can also be because of a number of other disorders or to a developmental process causing irregular bony growth. The adolescent presenting with FAI is athletic, particularly in endeavors placing excessive stress on the hip and surrounding soft tissues. The pain is characterized as sharp, localized around the anatomic femoral head location, and may be associated with catching or popping. Complete physical examination includes full range of motion testing, as a hallmark of FAI is restriction and pain with internal rotation. Special tests include the anterior impingement test, the FABER test, and the dial test. Imaging includes anteroposterior pelvic and cross-table lateral radiographs and magnetic resonance imaging. Treatment in all patients is 6 weeks of conservative therapy. If patients see no improvement with conservative treatment, they may be candidates for hip arthroscopy. Arthroscopic treatment of FAI includes rim trimming for pincer lesions, osteoplasty for cam decompression and labral detachment, and repair or reconstruction for labral tears. Studies have shown improvements in the modified Harris Hip Score and the Hip Outcomes Score postoperatively. As FAI is diagnosed most frequently in athletes, and it is estimated that 30 to 45 million adolescents 6 and 18 years old are involved in sports, it is becoming imperative to identify factors that may predict its development, study treatments, and improve outcomes.

Reproductive performance in the high-yielding dairy cow has severely decreased in the last 40 yr. The aim of this study was to compare the effectiveness of 4 nutritional strategies in improving the reproductive performance of high-yielding dairy cows. It was hypothesized that offering cows a high-starch ration in early lactation would enhance the onset of luteal activity, and that decreasing the severity of negative energy balance in the early postcalving period would improve reproductive parameters. Nutritional regimens aimed at improving fertility were applied to 96 Holstein-Friesian dairy animals. Upon calving, animals were allocated in a balanced manner to one of 4 dietary treatments. Primiparous animals were balanced according to live weight, body condition score and calving date. Multiparous animals were balanced according to parity, previous lactation milk yield, liveweight, body condition score and calving date. Treatment 1 was based on an industry best practice diet (control) to contain 170 g of crude protein/kg of dry matter. Treatment 2 was an individual cow feeding strategy, whereby the energy balance (EB) of individual animals was managed so as to achieve a predetermined target daily EB profile (±10 MJ/d). Treatment 3 was a high-starch/high-fat combination treatment, whereby an insulinogenic (high-starch) diet was offered in early lactation to encourage cyclicity and followed by a lipogenic (low-starch, high-fat) diet to promote embryo development. Treatment 4 was a low-protein diet, containing 140 g of crude protein/kg of dry matter, supplemented with protected methionine at an inclusion level of 40 g per animal per day. The nutritional strategies implemented in this study had no statistically significant effects on cow fertility measures, which included the onset of luteal activity, conception rate, in-calf rate, and the incidence of atypical cycles. The individual cow feeding strategy improved EB in early lactation but had no benefit on conception rate to first insemination. However, conception rate to second insemination, 100-d pregnancy rate (from the commencement of breeding), and overall pregnancy rate tended to be higher in this group. The high-starch/high-fat treatment tended to decrease the proportion of delayed ovulations and increase the proportion of animals cycling by d 50 postcalving. Animals that failed to conceive to first insemination had a significantly longer luteal phase in the first cycle postpartum and a longer inter-ovulatory interval in the second cycle postpartum. With regards to estrous behavior, results indicate that as the size of the sexually active group increased, the intensity of estrus and the expression of mounting or attempting to mount another cow also increased. Furthermore, cows that became pregnant displayed more intense estrous behavior than cows that failed to become pregnant., (Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The effects of the level of energy intake (high E and low E) offered before and after calving on body condition score at calving, production performance, and energy status in the first 250 d of lactation were evaluated in a 2 × 2 factorial design experiment involving 80 Holstein-Friesian dairy animals (40 primiparous and 40 multiparous). From d 80 until d 21 precalving, primiparous animals were offered either high or low pasture allowances. Thereafter, these animals were housed and had ad libitum access to a high energy density diet (high E) or restricted access [6 kg of dry matter (DM) per d] to a low energy density diet (low E), respectively, until calving. From d 100 until d 42 precalving, multiparous animals were offered either ad libitum or restricted (10 kg of DM/d) access to a late lactation diet, and thereafter, had ad libitum access to a high E diet or restricted access (7 kg of DM complete diet/d) to a low E diet, respectively, until calving. The forage to concentrate (F:C) ratios (DM basis) of these high E and low E diets [d 42 (d 21 in primiparous animals) until calving] were 64:36 and 83:17, respectively. Cows offered high E and low E precalving diets were allocated to either a high E or low E postcalving diet [F:C ratio (DM basis) of 30:70 and 70:30, respectively] and remained on these diets until d 250 of lactation. Multiparous animals offered a high E diet precalving had a significantly higher body condition score at calving than those offered the low E diet precalving. This effect was not evident in primiparous animals. Precalving diet had no significant effect on plasma nonesterified fatty acid concentrations during the last 3 wk precalving in primi- or multiparous animals. Primiparous animals offered a high E diet precalving had significantly higher postcalving plasma concentrations of nonesterified fatty acid, suggesting greater mobilization of body reserves. Primi- and multiparous animals offered a high E diet postcalving had a significantly higher dry matter intake, milk yield, and energy status postcalving compared with animals offered a low E diet postcalving. Milk yields of primiparous animals offered high E and low E diets postcalving were 29.7 and 24.8 kg/d, respectively, and milk yield of multiparous animals offered high E and low E diets postcalving were 33.5 and 28.2 kg/d, respectively. It is concluded that altering body condition score during the dry period is difficult but that specific dietary regimens applied precalving can have a significant influence on postcalving production and energy-related parameters., (Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The data set used in the present study was obtained from 20 energy metabolism studies involving 579 lactating dairy cows (511 Holstein-Friesian, 36 Norwegian Red, and 32 Jersey-Holstein crossbreds) varying in genetic merit, lactation number, stage of lactation, and live weight. These cows were offered diets based on grass silage (n=550) or fresh grass (n=29), and their energy intake and outputs, including methane energy (CH(4)-E), were measured in indirect open-circuit respiration calorimeter chambers. The objective was to use these data to evaluate relationships between CH(4)-E output and a range of factors in animal production and energetic efficiency in lactating dairy cows under normal feeding regimens. The CH(4)-E as a proportion of milk energy output (E(l)), E(l) adjusted to zero energy balance (E(l(0))), or intakes of gross energy (GE), digestible energy (DE), or metabolizable energy (ME) was significantly related to a wide range of variables associated with milk production (E(l) and E(l(0))) and energy parameters (energy intake, metabolizability, partitioning, and utilization efficiencies). Three sets of linear relationships were developed with experimental effects removed. The CH(4)-E/GE intake (r(2)=0.50-0.62) and CH(4)-E/E(l) (r(2)=0.41-0.68) were reduced with increasing feeding level, E(l)/metabolic body weight (MBW; kg(0.75)), E(l(0))/MBW, GE intake/MBW, DE intake/MBW, and ME intake/MBW. Increasing dietary ME/DE decreased CH(4)-E/E(l) (r(2)=0.46) and CH(4)-E/GE intake (r(2)=0.72). Dietary ME concentration and ME/GE were also negatively related to CH(4)-E/GE intake (r(2)=0.47). However, increasing heat production/ME intake increased CH(4)-E as a proportion of E(l) (r(2)=0.41), E(l(0)) (r(2)=0.67) and energy intake (GE, DE, and ME; r(2)=0.62 and 0.70). These proportional CH(4)-E variables were reduced with increasing ratios of E(l)/ME intake and E(l(0))/ME intake and efficiency of ME use for lactation (r(2)=0.49-0.70). Fitting CH(4)-E/E(l) or CH(4)-E/E(l(0)) against these energetic efficiencies in quadratic rather than linear relationships significantly increased r(2) values (0.49-0.67 vs. 0.59-0.87). In conclusion, CH(4)-E as a proportion of energy intake (GE, DE, and ME) and milk production (E(l) and E(l(0))) can be reduced by increasing milk yield and energetic efficiency of milk production or by reducing energy expenditure for maintenance. The selection of dairy cows with high energy utilization efficiencies and milk productivity offers an effective approach to reducing enteric CH(4) emission rates., (2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

This experiment examined the long-term effects of offering diets containing low levels of dietary phosphorus (P) on dairy cow health, fertility and bone composition, and the effect of dietary P level on nutrient utilisation. One hundred winter-calving Holstein-Friesian dairy cows were offered diets containing either 'high' or 'low' levels of dietary P over a 4-year period. Rations offered during the winter included grass silage, maize silage (70 : 30 dry matter (DM) basis, approximately) and concentrates (10.0 to 12.0 kg/cow per day). During the summer periods in years 1 and 2, half of the cows grazed both day and night, while the remaining cows grazed by day, and were housed by night and offered grass silage. During years 3 and 4, all cows grazed both day and night during the summer period. Concentrate feed levels during the summer periods were 3.0 to 4.0 kg/cow per day. Different dietary P levels were achieved by offering concentrates containing either high or low P levels during the winter period (approximately 7.0 or 4.4 g P/kg DM, respectively) and during the summer period (approximately 6.8 or 3.6 g P/kg DM, respectively). Total ration P levels averaged 4.9 and 3.6 g P/kg DM for the high and low P winter diets, respectively, and 4.2 and 3.6 g P/kg DM for the high and low P summer diets, respectively. A total of 95, 70, 50 and 22 cows completed each of lactations from 1 to 4, respectively. Neither the incidence of lameness or mastitis, or milk somatic cell count, were affected by dietary P level (P > 0.05), while none of the fertility parameters recorded in any of lactations from 1 to 4 was affected by the dietary P level (P > 0.05). Dietary P level had no effect on the specific gravity, ash or calcium content of rib cortical bone cores (n = 78 cows), while the P content of cortical bone (g/kg fresh, g/kg DM and mg/ml fresh bone) was lower with cows offered low P diets (P < 0.05). Dietary P level had no significant effect on the digestibility of either the DM, nitrogen, energy or acid detergent fibre fraction of the diet (P > 0.05), while faecal P excretions were reduced by a mean of 27 g/cow per day with cows offered the low P diets during the winter period. The results of this study indicate that dietary P levels can be reduced to proportionately 0.8 (approximately) of current UK feeding standards (Agricultural and Food Research Council, 1991), with no detrimental effect on dairy cow health or fertility, while having only minor effects on bone composition.

The loss of phosphates from dairy farms contributes to the eutrophication of waterways. Whilst reducing the phosphorus (P) content of dairy cow diets has the potential to help reduce phosphate losses, diets containing inadequate dietary P may have a negative effect on cow health and performance. To address this issue, 100 winter-calving Holstein-Friesian dairy cows were offered diets containing either 'high' or 'low' levels of dietary P. The experiment was conducted over a 4-year period, with 80 primiparous cows commencing the study in year 1, while a further 20 primiparous cows commenced the study in year 2. Rations offered during the winter comprised grass silage, maize silage (70 : 30 dry matter (DM) basis, approximately) and concentrates (10.0 to 12.0 kg/cow per day). During the summer periods in years 1 and 2, half of the cows grazed both day and night, while the remaining cows grazed by day, and were housed by night and offered grass silage. During years 3 and 4, all cows grazed both day and night during the summer period. Concentrate feed levels during the summer periods were 3.0 to 4.0 kg/cow per day. Different dietary P levels were achieved by offering concentrates containing either high or low P levels during the winter period (approximately 7.0 or 4.4 g P/kg DM respectively), and during the summer period (approximately 6.8 or 3.6 g P/kg DM, respectively). Total ration P levels averaged 4.9 and 3.6 g P/kg DM for the 'high' and 'low' P winter diets respectively, and 4.2 and 3.6 g P/kg DM for the 'high' and 'low' P summer diets respectively. A total of 95, 70, 50 and 22 cows completed each of lactations 1 to 4 respectively. Dietary P level had no significant effect on food intake, milk output or milk composition (P > 0.05). Plasma P concentrations were significantly lower with cows offered the 'low' P diet in each of lactations 1 to 4 (P < 0.05). In each of lactations 3 and 4, cows offered the 'low' P diet tended to have lower condition scores and live weights than those offered the 'high' P diet. The results of this experiment highlight that the P content of dairy cow diets can be substantially reduced with no detrimental effect on dairy cow performance.

Ninety autumn-calving Holstein dairy cows (45 primiparous and 45 multiparous; mean parity, 3.1) were allocated to 1 of 3 treatments; 173, 144, or 114 g of crude protein (CP)/kg of dry matter (DM) from calving until d 150 of lactation. On d 151 of lactation, half the animals receiving 114 g of CP/kg of DM went onto 144 g of CP/kg of DM, half of the animals receiving 144 g of CP/kg of DM went onto 173 g of CP/kg of DM, and half of the animals receiving 173 g of CP/kg of DM went onto 144 g of CP/kg of DM, with the remaining animals staying on their original treatments. This resulted in 6 treatments in mid to late lactation: 114/114; 144/144; 173/173; 114/144; 144/173; and 173/144 g of CP/kg of DM. Overall, 95.3% of cows intended for breeding conceived during a 6-mo breeding period. The average pregnancy rates to first service and first plus second service were 30.9% [standard error of the difference (SED), 0.05] and 56.7% (SED, 0.05) respectively. The average 100 d in-calf rate from the start of the breeding period was 70.5%, and at least one abnormal progesterone profile was observed in 62% of animals. An increase in dietary protein content decreased the requirement for treatment of metritis. There was no effect of dietary protein content on any of the reproductive or progesterone measures; for example, days to conception, calving interval, 100 d in-calf rate (from commencement of breeding), days to onset of luteal activity, average luteal phase, average interovulatory interval, or average interluteal interval. An increase in dietary protein content decreased the average daily energy balance. A more positive energy balance was associated with an increased requirement for the treatment of metritis in the current study. Cumulative energy balance was positively associated with conception. There was no effect of the concentration of plasma urea on any of the reproductive variables; however, the concentration of serum leptin was favorably associated with the time to progesterone increase above 3 ng/mL, which has been deemed essential for embryo survival. Additionally, the average peak concentration of progesterone and the duration of the average luteal phase were favorably associated with the interval from calving to conception. The latter relationships emphasize the importance of progesterone in achieving and maintaining pregnancy.

One of the main contributing factors to the decline in fertility in contemporary dairy farming is the inability to detect cows in estrus. In the current study, 90 Holstein dairy cows [45 primiparous and 45 multiparous (mean parity of 3.1)] were allocated to 1 of 3 treatments at calving; 173, 144, or 114 g of crude protein/kg of dry matter. Estrous behavior was recorded for one 30-min period every 12 h from calving until all animals reached 140 d postpartum. Behavioral activities were recorded according to a scoring system developed by Van Eerdenburg et al. (1996), with 9 key estrous behavioral activities each allocated a given number of points. If the total score allocated was greater than or equal to 50 points during a single or consecutive observational periods, then the animal was deemed to be in estrus. A total of 238 estrous cycles scored 50 points or above on the Van Eerdenburg et al. (1996) scale in this experiment, with 51.7% of these cycles being characterized as standing immobile on mounting. There were no direct effects of dietary protein content on estrous behavior; however, 3 significant stage of lactation x protein treatment interactions occurred for the behavioral activities (mucous discharge, chin resting, and mounting the head side of another cow), but no consistent trends were apparent from the predicted means. There was a significant influence of parity on the frequency of mounting the head side of another cow and total number of behavior activities displayed per estrous cycle. In both cases multiparous animals displayed fewer behavioral activities than primiparous animals. An increase in the size of the sexually active group (animals in estrus at the same time, up to 5) significantly increased the expression of mounting or attempting to mount another cow, the number of cycles in which standing immobile on being mounted was observed, the total estrous score and the proportion of cyclic animals that were diagnosed as being in estrus. The most frequent behavioral activity displayed was chin resting (89.5% of cycles), and the most reliable behavior was standing immobile on mounting (when expressed 96.4% of cows were in estrus). The most dependable (function of reliability and frequency displayed) sign of estrus was mounting or attempting to mount another cow. This behavior was expressed in 83% of cycles, and when expressed, 89% of animals were in estrus.

Ninety autumn-calving Holstein dairy cows [45 primiparous and 45 multiparous (mean parity, 3.1)] were allocated to 1 of 3 dietary crude protein (CP) concentrations: 173, 144, or 114 g of CP/kg of DM, from calving until d 150 of lactation. On d 151, half of the animals in each treatment were allocated an alternative dietary protein concentration. Half of the animals receiving 114 g of CP/kg of DM went onto 144 g of CP/kg of DM; half of the animals receiving 144 g of CP/kg of DM went onto 173 g of CP/kg of DM; and half of the animals receiving 173 g of CP/kg of DM went onto 144 g of CP/kg of DM, with the remaining animals staying on their original treatment. This resulted in 6 treatments in the mid to late lactation period: 114/114, 144/144, 173/173, 114/144, 144/173, and 173/144 g of CP/kg of DM. An increase in dietary CP concentration significantly increased milk, fat, and protein yield in early lactation (d 1 to 150). Dry matter intake was also increased with increased dietary protein concentration; however, this was not significant between 144 and 173 g of CP/kg of DM. Increased dietary CP significantly increased plasma urea, albumin, and total protein concentrations but had no significant effect on NEFA, leptin, or IGF-1 concentrations. Decreasing the dietary CP concentration in mid-late lactation (d 151 to 305) from 173 to 144 g/kg of DM had no significant effect on milk yield, dry matter intake, or milk fat and protein yield, compared with animals that remained on 173 g of CP/kg of DM throughout lactation. Increasing dietary CP concentration from 144 to 173 g/kg of DM significantly increased dry matter intake compared with animals that remained on the 144 g of CP/kg of DM throughout lactation. There were no significant dietary treatment effects on live weight or body condition score change throughout the experiment. Results of this study indicate that high protein diets (up to 173 g of CP/kg of DM) improved feed intake and animal performance in early lactation (up to d 150), but thereafter, protein concentration can be reduced to 144 g of CP/kg of DM with no detrimental effects on animal performance.

There is a paucity of data on the beef production potential of Norwegian Red (NOR) compared with 'modern' Holstein-Friesian (HF) cattle. The present study used a total of 64 bulls in a 2 × 2 factorial design study encompassing two breeds (HF and NOR) and two slaughter ages (485; E, and 610; L, days). The mean initial age and live weight of the HF bulls were 179 (s.d. 47.1) days and 203 (s.d. 64.0) kg, while the corresponding data for the NOR bulls were 176 (s.d. 39.7) days and 185 (s.d. 63.6) kg, respectively. Bulls were offered a 50 : 50 mixture (dry matter (DM) basis) of grass silage and concentrates. No breed × slaughter group interactions were recorded for any parameters evaluated (P > 0.05). HF bulls had higher (P < 0.001) DM intake and poorer (P < 0.01) efficiency of conversion of food to carcass gain than NOR bulls. HF bulls tended (P = 0.07) to have a higher rate of live-weight gain and were heavier (P < 0.001) at slaughter than NOR bulls, though both carcass weight and rate of carcass gain did not differ between the breeds (P > 0.05). NOR bulls had higher (P < 0.001) dressing proportion and carcass conformation score than HF bulls, while breed of bull had no influence (P > 0.05) on carcass fat classification, depth of subcutaneous fat, marbling score or on the weight of fat in the internal depots. Daily food intakes did not differ (P > 0.05) across the two slaughter age groups, though efficiency of conversion of food to carcass gain was poorer (P < 0.05) in the L compared with E bulls. Rate of live-weight gain was lower (P < 0.01) for L bulls, although rate of carcass gain did not differ (P > 0.05) between the E and L bulls. Increasing age at slaughter increased (P < 0.01 or greater) dressing proportion, carcass fat class, depth of subcutaneous fat, marbling score and internal fat depots, but had no effect (P > 0.05) on the carcass conformation score. Instrumental measures of meat quality indicated that meat from NOR bulls was tougher (P < 0.01) than meat from HF bulls, while delaying slaughter increased (P < 0.001) a* and C*ab, and decreased (P < 0.01) h0, indicating improved redness. It is concluded that NOR bulls have higher food efficiency and produce more highly conformed carcasses than HF bulls, but HF bulls produce more tender meat.

The objective of the present study was to investigate the potential of the urea dilution technique, coupled with live animal measures to predict the body components of dairy cattle. The study involved 104 lactating Holstein-Friesian cows offered grass silage-based diets. Urea space volume (USV) was calculated from 2 collection periods of blood samples following infusion of urea at 12 (USV12, kg) and 30 (USV30, kg) min after infusion, and then as a proportion of live weight (LW) or empty body weight (EBW). All cows were slaughtered within 2 d of the USV trials. Large ranges existed in EBW and empty body concentrations of water, crude protein (CP), lipid, ash, and gross energy (GE). The USV12 and USV30 were both positively related to LW, EBW, and empty body component weights. The r2 values for USV12 were greater than USV30. The r2 values in the relationships of EBW and empty body composition with USV, however, were smaller than those with LW. Nevertheless, the relationships were improved when both USV and LW were used as predictors, rather than using either alone. Adding milk yield and body condition score as supporting predictors to prediction equations using USV and LW data for EBW, lipid, and GE contents further improved the relationships (r2 = 0.93, 0.66, and 0.77, respectively). Internal evaluation of one-third of the present data using equations developed from two-thirds of the present data indicated that using USV, live weight, and other live animal variables as predictors, rather than using USV alone, considerably improved the prediction accuracy. It was concluded that USV can be used to predict body composition, but the relationships with USV were poorer than those with LW. The USV can only be used as a supporting variable to live weight for prediction of body components in lactating dairy cows.