Fundamentals of OA. An initiative of Osteoarthritis and Cartilage. Obesity and metabolic factors in OA.

OBJECTIVE: Obesity was once considered a risk factor for knee osteoarthritis (OA) primarily for biomechanical reasons. Here we provide an additional perspective by discussing how obesity also increases OA risk by altering metabolism and inflammation. DESIGN: This narrative review is presented in four sections: 1) metabolic syndrome and OA, 2) metabolic biomarkers of OA, 3) evidence for dysregulated chondrocyte metabolism in OA, and 4) metabolic inflammation: joint tissue mediators and mechanisms. RESULTS: Metabolic syndrome and its components are strongly associated with OA. However, evidence for a causal relationship is context dependent, varying by joint, gender, diagnostic criteria, and demographics, with additional environmental and genetic interactions yet to be fully defined. Importantly, some aspects of the etiology of obesity-induced OA appear to be distinct between men and women, especially regarding the role of adipose tissue. Metabolomic analyses of serum and synovial fluid have identified potential diagnostic biomarkers of knee OA and prognostic biomarkers of disease progression. Connecting these biomarkers to cellular pathophysiology will require future in vivo studies of joint tissue metabolism. Such studies will help reveal when a metabolic process or a metabolite itself is a causal factor in disease progression. Current evidence points towards impaired chondrocyte metabolic homeostasis and metabolic-immune dysregulation as likely factors connecting obesity to the increased risk of OA. CONCLUSIONS: A deeper understanding of how obesity alters metabolic and inflammatory pathways in synovial joint tissues is expected to provide new therapeutic targets and an improved definition of "metabolic" and "obesity" OA phenotypes.

Can a Reduction in Revision Rates Make Robotic Total Knee Arthroplasty Cost Neutral With Manual Total Knee Arthroplasty at Ten-Year Follow-Up? An Episode Cost Analysis.

BACKGROUND: Advocates of robotic total knee arthroplasty (RTKA) suggest that its greater cost may be recaptured through a reduction in revision rates. We sought to determine what reduction in revision TKA would be required for RTKA to become cost neutral with manual TKA (MTKA). METHODS: Episode costs were determined for 2392 RTKAs and 2392 MTKAs. Mean total cost of revision TKA in our health system was identified. Episode cost difference of the RTKA and MTKA cohorts was divided by the mean cost of revision TKA to estimate the reduction in revisions required to make RTKA cost neutral with MTKA. The National Joint Registry was consulted to determine the cumulative revision rate for the implant used in this study. RESULTS: Episode cost for the RTKA cohort was $5.7M greater than MTKA. Mean acute stay cost for revision TKA was $20,972, but post-acute costs were not available. If post-acute costs for revision TKA are conservatively estimated at 50% of episode cost (ie, episode cost = $41,944), 131 revision TKAs would need to be prevented in the RTKA cohort to make it cost neutral with MTKA. The National Joint Registry cumulative revision rate for this implant is 3.37% at 10 years, thus only 81 revisions would be expected per cohort. CONCLUSION: Our data suggest that it is not possible for RTKA to achieve cost parity with MTKA through a reduction in revision rate alone. Future price reductions may make the cost comparison more favorable. In addition, demonstration of improved patient outcomes would undeniably add value to RTKA and change the analysis.

Robotic Versus Manual Total Knee Arthroplasty in High Volume Surgeons: A Comparison of Cost and Quality Metrics.

BACKGROUND: Robotic-assisted total knee arthroplasty (RTKA) was introduced to improve surgical accuracy and patient outcomes. However, RTKA may also increase operating time and add cost to TKA. This study sought to compare the differences in cost and quality measures between manual TKA (MTKA) and RTKA METHODS: All MTKAs and RTKAs performed between January 1, 2017 and December 31, 2019, by 6 high volume surgeons in each cohort, were retrospectively reviewed. Cohorts were propensity score matched. Operative time, length of stay (LOS), total direct cost, 90-day complications, utilization of postacute services, and 30-day readmissions were studied. RESULTS: After one-to-one matching, 2392 MTKAs and 2392 RTKAs were studied. In-room/out-of-room operating time was longer for RTKA (139 minutes) than for MTKA (107 minutes) P < .0001, as was procedure time (RTKA 78 minutes; MTKA 70 minutes), P < .0001. Median LOS was equal for MTKA and RTKA (33 hours). Total cost per case was greater for RTKA ($11,615) than MTKA ($8674), P < .0001. Home health care was utilized more frequently after RTKA (38%) than MTKA (29%), P < .0001. There was no significant difference in 90-day complication rates. Thirty-day readmissions occurred more often after MTKA (4.9%) than RTKA (1.2%), P < .0001. CONCLUSION: RTKA was a longer and costlier procedure than MTKA for experienced surgeons, without clinically significant differences in LOS or complications. Home health care was utilized more often after RTKA, but fewer readmissions occurred after RTKA. Longer term follow-up and functional outcome studies are required to determine if the greater cost of RTKA is offset by lower revision rates and/or improved functional results.

Effects of long-term exercise and a high-fat diet on synovial fluid metabolomics and joint structural phenotypes in mice: an integrated network analysis.

OBJECTIVE: To explore how systemic factors that modify knee osteoarthritis risk are connected to 'whole-joint' structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics. METHODS: Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9-13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group. RESULTS: High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1ß and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites. CONCLUSION: Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.

A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

A Rare Case of Infertility: SRY Positive 46, XX Testicular Disorder of Sexual Differentiation.

Aim To highlight the complexity of infertility causes by describing the rare case of a man with a testicular disorder of sexual differentiation. Diagnosis A 33 years old Caucasian male presented with a 3-year-old history of primary infertility. His investigations revealed a low testosterone and a raised LH and FSH levels. A sample sent for sperm analysis revealed azoospermia. Chromosomal analysis and karyotyping revealed a 46 XX SRY positive karyotype. Treatment The patient was initiated on testosterone replacement and on calcium/vitamin D supplements. Conclusion Fertility evaluation requires complex assessments and a broad knowledge of possible causes.

GC-MS method for metabolic profiling of mouse femoral head articular cartilage reveals distinct effects of tissue culture and development.

OBJECTIVE: The metabolic profile of cartilage is important to define as it relates to both normal and pathophysiological conditions. Our aim was to develop a precise, high-throughput method for gas/chromatography-mass/spectrometry (GC-MS) semi-targeted metabolic profiling of mouse cartilage. METHOD: Femoral head (hip) cartilage was isolated from 5- and 15-week-old male C57BL/6J mice immediately after death for in vivo analyses. In vitro conditions were evaluated in 5-week-old samples cultured ±10% fetal bovine serum (FBS). We optimized cartilage processing for GC-MS analysis and evaluated group-specific differences by multivariate and parametric statistical analyses. RESULTS: 55 metabolites were identified in pooled cartilage (4 animals per sample), with 29 metabolites shared between in vivo and in vitro conditions. Multivariate analysis of these common metabolites demonstrated that culturing explants was the strongest factor altering cartilage metabolism, followed by age and serum starvation. In vitro culture altered the relative abundance of specific metabolites; whereas, cartilage development between five and 15-weeks of age reduced the levels of 36 out of 43 metabolites >2-fold, especially in TCA cycle and alanine, aspartate, and glutamate pathways. In vitro serum starvation depleted six out of 41 metabolites. CONCLUSION: This study describes the first GC-MS method for mouse cartilage metabolite identification and quantification. We observed fundamental differences in femoral head cartilage metabolic profiles between in vivo and in vitro conditions, suggesting opportunities to optimize in vitro conditions for studying cartilage metabolism. In addition, the reductions in TCA cycle and amino acid metabolites during cartilage maturation illustrate the plasticity of chondrocyte metabolism during development.

Process evaluation results of a cluster randomised controlled childhood obesity prevention trial: the WAVES study.

BACKGROUND: Increasing prevalence of childhood obesity and its related consequences emphasises the importance of developing and evaluating interventions aimed at prevention. The importance of process evaluation in health intervention research is increasingly recognised, assessing implementation and participant response, and how these may relate to intervention success or failure. A comprehensive process evaluation was designed and undertaken for the West Midlands ActiVe lifestyle and healthy Eating in School children (WAVES) study that tested the effectiveness of an obesity prevention programme for children aged 6-7 years, delivered in 24 UK schools. The four intervention components were: additional daily school-time physical activity (PA); cooking workshops for children and parents; Villa Vitality (VV), a 6-week healthy lifestyle promotion programme run by a local football club; and signposting to local PA opportunities. METHODS: Data relating to six dimensions (Fidelity, Reach, Recruitment, Quality, Participant Responsiveness, Context) were collected via questionnaires, logbooks, direct observations, focus groups and interviews. Multiple data collection methods allowed for data triangulation and validation of methods, comparing research observations with teacher records. The 6-stage WAVES study model ((i) Data collection, (ii) Collation, (iii) Tabulation, (iv) Score allocation and discussion, (v) Consultation, (vi) Final score allocation) was developed to guide the collection, assimilation and analysis of process evaluation data. Two researchers independently allocated school scores on a 5-point Likert scale for each process evaluation dimension. Researchers then discussed school score allocations and reached a consensus. Schools were ranked by total score, and grouped to reflect low, medium or high intervention implementation. RESULTS: The intervention was predominantly well-implemented and well-received by teachers, parents and children. The PA component was identified as the most challenging, VV the least. Median implementation score across schools was 56/75 (IQR, 51.0 - 60.8). Agreement between teacher logbooks and researcher observations was generally high, the main discrepancies occurred in session duration reporting where in some cases teachers' estimations tended to be higher than researchers'. CONCLUSIONS: The WAVES study model provides a rigorous and replicable approach to undertaking and analysing a multi-component process evaluation. Challenges to implementing school-based obesity prevention interventions have been identified which can be used to inform future trials. TRIAL REGISTRATION: ISRCTN97000586 . 19 May 2010.

Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC. PATIENTS AND METHODS: Patients (N = 297) were stratified by the number of prior therapies for metastatic disease (0-1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1 : 1 : 1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E). Each treatment arm was well balanced with regard to the proportion of patients with AR-positive breast cancer. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, clinical benefit rate, duration of response, and overall response rate. RESULTS: There was no significant difference in PFS with AA versus E (3.7 versus 3.7 months; hazard ratio [HR] = 1.1; 95% confidence interval [CI] 0.82-1.60; P = 0.437) or AAE versus E (4.5 versus 3.7 months; HR = 0.96; 95% CI 0.70-1.32; P = 0.794). Increased serum progesterone concentrations were observed in both arms receiving AA, but not with E. Grade 3 or 4 treatment-emergent adverse events associated with AA, including hypokalemia and hypertension, were less common in patients in the E (2.0% and 2.9%, respectively) and AA arms (3.4% and 1.1%, respectively) than in the AAE arm (5.8% for both). CONCLUSIONS: Adding AA to E in NSAI-pretreated ER+ MBC patients did not improve PFS compared with treatment with E. An AA-induced progesterone increase may have contributed to this lack of clinical activity. CLINICALTRIALSGOV: NCT01381874.

Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials.

BACKGROUND: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. PATIENTS AND METHODS: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. RESULTS: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostate-specific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. CONCLUSION: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. CLINICAL TRIALS NUMBER: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).

Salivary proteomics in bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVE: The objective of this study was to identify differentially expressed salivary proteins in bisphosphonate-related osteonecrosis of the jaw (BRONJ) patients that could serve as biomarkers for BRONJ diagnosis. SUBJECTS AND METHODS: Whole saliva obtained from 20 BRONJ patients and 20 controls were pooled within groups. The samples were analyzed using iTRAQ-labeled two-dimensional liquid chromatography-tandem mass spectrometry. RESULTS: Overall, 1340 proteins were identified. Of these, biomarker candidates were selected based on P-value (<0.001), changes in protein expression (≥1.5-fold increase or decrease), and unique peptides identified (≥2). Three comparisons made between BRONJ and control patients identified 200 proteins to be differentially expressed in BRONJ patients. A majority of these proteins were predicted to have a role in drug metabolism and immunological and dermatological diseases. Of all the differentially expressed proteins, we selected metalloproteinase-9 and desmoplakin for further validation. Immunoassays confirmed increased expression of metalloproteinase-9 in individual saliva (P = 0.048) and serum samples (P = 0.05) of BRONJ patients. Desmoplakin was undetectable in saliva. However, desmoplakin levels tended to be lower in BRONJ serum than controls (P = 0.157). CONCLUSIONS: Multiple pathological reactions are involved in BRONJ development. One or more proteins identified by this study may prove to be useful biomarkers for BRONJ diagnosis. The role of metalloproteinase-9 and desmoplakin in BRONJ requires further investigation.

Metabolic enrichment of omega-3 polyunsaturated fatty acids does not reduce the onset of idiopathic knee osteoarthritis in mice.

OBJECTIVE: We evaluated the effect of a reduction in the systemic ratio of n-6:n-3 polyunsaturated fatty acids (PUFAs) on changes in inflammation, glucose metabolism, and the idiopathic development of knee osteoarthritis (OA) in mice. We hypothesized that a lower ratio of n-6:n-3 PUFAs would protect against OA markers in cartilage and synovium, but not bone. DESIGN: Male and female fat-1 transgenic mice (Fat-1), which convert dietary n-6 to n-3 PUFAs endogenously, and their wild-type (WT) littermates were fed an n-6 PUFA enriched diet for 9-14 months. The effect of gender and genotype on serum PUFAs, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and glucose tolerance was tested by 2-factor analysis of variance (ANOVA). Cortical and trabecular subchondral bone changes were documented by micro-focal computed tomography (CT), and knee OA was assessed by semi-quantitative histomorphometry grading. RESULTS: The n-6:n-3 ratio was reduced 12-fold and 7-fold in male and female Fat-1 mice, respectively, compared to WT littermates. IL-6 and TNF-α levels were reduced modestly in Fat-1 mice. However, these systemic changes did not reduce osteophyte development, synovial hyperplasia, or cartilage degeneration. Also the fat-1 transgene did not alter subchondral cortical or trabecular bone morphology or bone mineral density. CONCLUSIONS: Reducing the systemic n-6:n-3 ratio does not slow idiopathic changes in cartilage, synovium, or bone associated with early-stage knee OA in mice. The anti-inflammatory and anti-catabolic effects of n-3 PUFAs previously reported for cartilage may be more evident at later stages of disease or in post-traumatic and other inflammatory models of OA.

Gingival crevicular fluid levels of interferon-γ, but not interleukin-4 or -33 or thymic stromal lymphopoietin, are increased in inflamed sites in patients with periodontal disease.

OBJECTIVE: To investigate the hypothesis that levels of interferon (IFN)-γ and interleukin (IL)-4, as well as the newer cytokines IL-33 and thymic stromal lymphopoietin (TSLP), in gingival crevicular fluid (GCF) samples differ from sites of patients at various clinical stages of periodontal disease and controls. BACKGROUND: Periodontal diseases result from the complex interplay between pathogenic bacteria and the host's immune responses. Several inflammatory mediators, such as IFN-γ and IL-4, have been detected in GCF samples in patients with periodontitis, but the results are mostly contradicting due to the lack of uniformity and collection of sites and methods of analysis. MATERIAL AND METHODS: GCF samples were collected from sites with different clinical characteristics (healthy, gingivitis and periodontitis sites) from periodontally healthy ( n = 14), plaque-induced gingivitis (n = 17) and chronic periodontitis (n = 11) subjects. The GCF samples were analyzed for the frequency of detection and levels of IFN-γ, IL-4, IL-33 and TSLP using a multiplex bead immunoassay. RESULTS: Inflamed sites in both patients with plaque-induced gingivitis and chronic periodontitis showed statistically significantly higher volume of GCF compared to non-inflamed sites in all patients. IFN-γ could be detected in about 50-70% of the samples analyzed and at significantly higher levels in sites with periodontitis compared to healthy sites in patients with chronic periodontitis (p = 0.035). We also show a statistically significant decrease of IFN-? in healthy sites of patients with chronic periodontitis as compared to gingivitis sites in patients with plaque-induced gingivitis (p = 0.047). Only some of the GCF samples showed detectable levels for IL-4 and TSLP, while IL-33 was below the detection level in all samples collected. CONCLUSIONS: These results suggest that IFN-γ levels in GCF depend on the clinical stage of the site and not on the disease stage of the patient, but need to be expanded to a greater number of subjects and additional analysis of corresponding gingival tissue biopsies for cytokine gene expression.

Effect of supplementing algae to breeding and early gestation first calf heifers on growth and reproduction.

Fat supplementation has potential to improve reproductive performance and increase pregnancy rates in cattle by increasing the energy density of the diet. However, some of the positive effects of fat seem to be influenced by the type of fatty acid fed. Docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) are long-chain n-3 poly-unsaturated fatty acids (PUFA) that have important biological effects on reproduction through their involvement in hormone and series 3 prostaglandin synthesis. Ruminant tissues are naturally almost devoid of n-3 long-chain PUFA, specifically EPA and DHA. Algae biomass provides a consistent source of DHA and EPA that could be fed to alter hormonal profiles and improve reproduction of beef heifers. Eighty-eight Angus × Simmental heifers (427 ±â€…1.8 kg body weight [BW]) were blocked by BW and allotted to 2 treatments (44/treatment, 4 pens/treatment, 11 heifers/pen). Control heifers were fed a diet that contained (dry matter [DM] basis) 52.8% mixed grass silage, 32% corn silage, and 15.2% concentrate. DHAgold (49% fat; 21.8% DHA; DSM Inc.) was included in the algae diet at 1.65% DM, replacing equal parts of corn and DDGS. Diets were formulated to contain 12% crude protein and 0.85 Mcal/kg net energy for gain (NEg). Heifers were fed treatment diets from 54 d prior to the breeding season through the first trimester. Follicular fluid was collected on day 47 for hormonal analysis. Artificial insemination (AI) was from days 54 to 77. Heifers that did not get pregnant to AI were removed from the study on day 109 and placed with a bull. The study ended on day 180. Data were analyzed using the MIXED procedure of SAS. During the pre-breeding period, algae heifers had lesser dry matter intake (P = 0.006) compared to control heifers. Heifers supplemented with algae had a greater average daily gain (P = 0.03) during the breeding period and BW tended (P = 0.06) to be greater for algae compared to control heifers on day 98 and was greater on day 180 (P = 0.03). Dominant follicle diameter and follicular estrogen concentration were unaffected by treatment (P ≥ 0.12). Follicular insulin-like growth factor-1 was greater in algae compared to control heifers (P = 0.03). First service conception rate did not differ between treatments (P = 0.67); however, second service and overall conception were lesser (P ≤ 0.03) in algae compared to control heifers. These data suggest supplementing DHA-rich algae improved growth but decreased conception rates of primiparous beef females.

Docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) are long-chain omega-3 poly-unsaturated fatty acids (PUFA) that have important biological effects on reproduction through their involvement in hormone and series 3 prostaglandin synthesis. Ruminant tissues are naturally almost devoid of omega-3 long-chain PUFA, specifically EPA and DHA. Algae biomass provides a consistent source of DHA and EPA that could be fed to alter hormonal profiles and improve reproduction of beef heifers. Therefore the objective of this study was to determine the effect of DHA-rich microalgae (Schizochytrium sp.) supplementation from 54 d prior to and 126 d after breeding on growth and reproduction of first calf heifers. Results from the current study indicate that the inclusion of microalgae in the diet of first calf beef heifers during the breeding season improves body weight and progeny birth weights, but negatively impacts reproduction. Omega-3 fatty acid inhibition of PGF2α secretion during the breeding season of algae-fed heifers may have delayed development of new follicles, ovulation, and behavioral estrus.

Fetal sex effects on maternal health can now be tested via randomization: A first-in-class illustration in cows on glucoregulatory outcomes.

BACKGROUND: The maternal-offspring relationship, such as whether fetal sex influences maternal health, is essential to explore to advance prenatal and maternal health. While associations exist between fetal sex and maternal health outcomes, it is unclear whether these reflect a causal relationship. OBJECTIVE: To demonstrate that fetal sex can be randomly assigned to test the causal effect of fetal sex on maternal outcomes. METHODS: Holstein dairy cows were stratified and randomized using sealed opaque envelopes to be artificially inseminated with either X- or Y-sorted bull semen until 40 cows became pregnant. Monthly body weight measurements were recorded, and an intravenous glucose tolerance test was performed 30 days before the expected calving day. The primary outcome was insulin area under the curve (AUC), and secondary outcomes were clearance rate, half-life, and AUC for glucose, insulin, and non-esterified fatty acid concentrations. An intention-to-treat (ITT) approach using multiple imputation was employed for primary analysis, and an as-treated (AT) approach was used for secondary analysis. RESULTS: We demonstrated that we could successfully randomize the assignment of fetal sex to dams and test for causal effects of fetal sex on glucoregulatory outcomes using dairy cows as a model. Insulin AUC was not statistically different between groups (ITT p = 0.857, AT p = 0.874), and other outcomes were also not statistically different (p > 0.05). CONCLUSION: We demonstrated that causal effects of fetal sex on maternal outcomes can be causally tested in dairy cows. Our study did not provide statistical evidence to support an effect of fetal sex on maternal glucose-related outcomes.

Case-Study Investigation of Equine Maternity via PCR-RFLP: A Biochemistry Laboratory Experiment.

A simple and robust biochemistry laboratory experiment is described that uses restriction fragment length polymorphism (RFLP) of polymerase chain reaction (PCR) products to verify the identity of a potentially valuable horse. During the first laboratory period, students purify DNA from equine samples and amplify two loci of mitochondrial DNA. During the second laboratory period, students digest PCR products with restriction enzymes and analyze the fragment sizes through agarose gel electrophoresis. An optional step of validating DNA extracts through realtime PCR can expand the experiment to three weeks. This experiment, which has an engaging and versatile scenario, provides students with exposure to key principles and techniques of molecular biology, bioinformatics, and evolution in a forensic context.

Home Exercise Programs Are Infrequently Prescribed in Trials of Supervised Exercise for Individuals With Low Back Pain: A Scoping Review of 292 Randomized Controlled Trials.

OBJECTIVES: To (1) determine how often home exercise programs (HEPs) are prescribed in supervised exercise trials for low back pain (LBP) and (2) describe characteristics of the HEP programs (design, purpose, dose, and adherence). DESIGN: Scoping review. LITERATURE SEARCH: PubMed, CINAHL, and Ovid MEDLINE were searched from January 1, 2010, to August 17, 2021. STUDY SELECTION CRITERIA: Randomized controlled trials that included adults with LBP who received exercise interventions. DATA SYNTHESIS: The presence or absence of a prescribed HEP and any details of the HEP including design, dose, and adherence were extracted and summarized. RESULTS: Of 2689 potentially relevant trials, 292 were eligible for inclusion. Ninety-four trials (32%) included a HEP. The most commonly prescribed home exercises were core stability, trunk strengthening, and motor control exercises. There was great variation in the frequency and duration with which HEPs were prescribed. Adherence to HEPs was measured in fewer than half of the trials, and the methods for measuring adherence were inconsistent. Adherence to HEPs ranged from 29% to 82% in the 21 trials that reported adherence. CONCLUSION: Home exercise programs are not regularly prescribed in supervised exercise trials for LBP. There was considerable variation in prescribing HEPs and monitoring exercise adherence in trials of exercise-based treatments for adults with LBP. There is no consistent method used to measure participants' adherence to HEPs, and adherence percentages vary widely. J Orthop Sports Phys Ther 2023;53(3):120-142. Epub: 16 January 2023. doi:10.2519/jospt.2023.11448.