Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors.

Irisin is secreted by muscle, increases with exercise, and mediates certain favorable effects of physical activity. In particular, irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear, and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the αV class of integrins, and biophysical studies identify interacting surfaces between irisin and αV/ß5 integrin. Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of FNDC5 (or irisin) completely blocks osteocytic osteolysis induced by ovariectomy, preventing bone loss and supporting an important role of irisin in skeletal remodeling. Identification of the irisin receptor should greatly facilitate our understanding of irisin's function in exercise and human health.

Deletion of mouse lysyl oxidase in megakaryocytes affects bone properties in a sex-dependent manner.

ABSTRACT: Lysyl oxidase (LOX) is a facilitator of extracellular matrix cross-linking. Using newly developed megakaryocyte-specific LOX knockout mice, we show that LOX expressed in these scarce bone marrow cells affects bone volume and collagen architecture in a sex-dependent manner.

Structure-based design of selective, orally available salt-inducible kinase inhibitors that stimulate bone formation in mice.

Osteoporosis is a major public health problem. Currently, there are no orally available therapies that increase bone formation. Intermittent parathyroid hormone (PTH) stimulates bone formation through a signal transduction pathway that involves inhibition of salt-inducible kinase isoforms 2 and 3 (SIK2 and SIK3). Here, we further validate SIK2/SIK3 as osteoporosis drug targets by demonstrating that ubiquitous deletion of these genes in adult mice increases bone formation without extraskeletal toxicities. Previous efforts to target these kinases to stimulate bone formation have been limited by lack of pharmacologically acceptable, specific, orally available SIK2/SIK3 inhibitors. Here, we used structure-based drug design followed by iterative medicinal chemistry to identify SK-124 as a lead compound that potently inhibits SIK2 and SIK3. SK-124 inhibits SIK2 and SIK3 with single-digit nanomolar potency in vitro and in cell-based target engagement assays and shows acceptable kinome selectivity and oral bioavailability. SK-124 reduces SIK2/SIK3 substrate phosphorylation levels in human and mouse cultured bone cells and regulates gene expression patterns in a PTH-like manner. Once-daily oral SK-124 treatment for 3 wk in mice led to PTH-like effects on mineral metabolism including increased blood levels of calcium and 1,25-vitamin D and suppressed endogenous PTH levels. Furthermore, SK-124 treatment increased bone formation by osteoblasts and boosted trabecular bone mass without evidence of short-term toxicity. Taken together, these findings demonstrate PTH-like effects in bone and mineral metabolism upon in vivo treatment with orally available SIK2/SIK3 inhibitor SK-124.

Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies.

Biallelic pathogenic variants in MAP3K20, which encodes a mitogen-activated protein kinase, are a rare cause of split-hand foot malformation (SHFM), hearing loss, and nail abnormalities or congenital myopathy. However, heterozygous variants in this gene have not been definitively associated with a phenotype. Here, we describe the phenotypic spectrum associated with heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20. We report five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in this specific region of the gene. These individuals exhibit both shared and unique clinical manifestations, highlighting the complexity and variability of the disorder. We propose that the involvement of MAP3K20 in endothelial-mesenchymal transition provides a plausible etiology of these features. Together, these findings characterize a disorder that both expands the phenotypic spectrum associated with MAP3K20 and highlights the need for further studies on its role in early human development.

miR-15a/16-1 deletion in activated B cells promotes plasma cell and mature B-cell neoplasms.

Chromosome 13q deletion [del(13q)], harboring the miR-15a/16-1 cluster, is one of the most common genetic alterations in mature B-cell malignancies, which originate from germinal center (GC) and post-GC B cells. Moreover, miR-15a/16 expression is frequently reduced in lymphoma and multiple myeloma (MM) cells without del(13q), suggesting important tumor-suppressor activity. However, the role of miR-15a/16-1 in B-cell activation and initiation of mature B-cell neoplasms remains to be determined. We show that conditional deletion of the miR-15a/16-1 cluster in murine GC B cells induces moderate but widespread molecular and functional changes including an increased number of GC B cells, percentage of dark zone B cells, and maturation into plasma cells. With time, this leads to development of mature B-cell neoplasms resembling human extramedullary plasmacytoma (EP) as well as follicular and diffuse large B-cell lymphomas. The indolent nature and lack of bone marrow involvement of EP in our murine model resembles human primary EP rather than MM that has progressed to extramedullary disease. We corroborate human primary EP having low levels of miR-15a/16 expression, with del(13q) being the most common genetic loss. Additionally, we show that, although the mutational profile of human EP is similar to MM, there are some exceptions such as the low frequency of hyperdiploidy in EP, which could account for different disease presentation. Taken together, our studies highlight the significant role of the miR-15a/16-1 cluster in the regulation of the GC reaction and its fundamental context-dependent tumor-suppression function in plasma cell and B-cell malignancies.

Outcomes of psychological support skills training for cancer care staff: Skill acquisition, work engagement, mental wellbeing and burnout.

OBJECTIVE: Psychological support skills training has the potential to improve both the ability of cancer staff to help their patients, and staff wellbeing. However, few recent studies have assessed both these outcomes or incorporated current developments in psychological skills training, such as deliberate practice, which includes the use of iterative, corrective feedback to identify and improve individualised skill deficits. No studies have evaluated the contribution that psychological skills training could make to cancer care staff wellbeing and expertise in the wake of the COVID-19 pandemic. This study aimed to evaluate staff skill acquisition and work-related wellbeing following psychological support skills training that applied deliberate practice principles. METHOD: A 2-day training and monthly supervision was offered to 145 cancer care staff that focused on brief assessment and intervention skills for patients experiencing mental health problems after cancer diagnosis and treatment. Deliberate practice principles were used to focus training on skills practice and feedback, over technique description. Self-reported ability to perform key skills taught, staff mental wellbeing, work engagement, and burnout were assessed at baseline, 3-month and 8-month follow-up. RESULTS: Significant improvements in skills, mental wellbeing, burnout and work engagement were reported at 8-month follow-up. Full engagement in both training sessions was predicted by poorer baseline mental wellbeing, more positive evaluation of initial training, supervision attendance, and shorter follow-up. CONCLUSION: A 2-day psychological support skills training using deliberate practice principles may support improvement in staff skill, mental wellbeing, burnout and work engagement.

Reduced versus standard intradetrusor OnabotulinumtoxinA injections for treatment of overactive bladder.

BACKGROUND: Intradetrusor onabotulinumtoxinA injection is an effective advanced treatment for overactive bladder. While the effective dosages have been well studied, very little data exist on treatment efficacy using differing injection techniques. The objective of this study was to determine whether the efficacy of a reduced injection technique of 5 injection sites was noninferior to the standard technique of 20 injection sites of intradetrusor onabotulinumtoxinA for treatment of overactive bladder. METHODS: In this randomized noninferiority trial, men and women seeking treatment of overactive bladder with intradetrusor onabotulinumtoxinA injections were randomized to receive 100 units administered via either a reduced injection technique of 5 injection sites or a standard injection technique of 20 injection sites. Subjects completed a series of standardized questionnaires at baseline and at 4-12 weeks postprocedure to determine symptom severity and treatment efficacy. The primary outcome was treatment efficacy as determined by Overactive Bladder Questionnaire-Short Form with a noninferiority margin of 15 points. Secondary outcomes were incidence of urinary tract infection and urinary retention requiring catheterization. RESULTS: Data from 77 subjects were available for analysis with 39 in the control arm (20 injections) and 38 in the study arm (5 injections). There was a significant improvement in both arms from baseline to follow-up in Overactive Bladder Questionnaire-Short Form and International Consultation on Incontinence Questionnaire scores (p < 0.001). Overall treatment success was 68% with no statistically significant difference between arms. A significant difference between arms was found on the Overactive Bladder Questionnaire-Short Form quality of life survey favoring the control arm (confidence interval [CI]: 0.36-20.5, p = 0.04). However, there were no significant differences between arms in the remaining validated questionnaires. The study arm did not demonstrate noninferiority to the control arm. Subjects in the study arm were significantly more likely to express a willingness to undergo the procedure again (odds ratio = 3.8, 95% CI: 1.42-10.67, p = 0.004). Adverse events did not differ between arms. CONCLUSIONS: A reduced injection technique for administration of intradetrusor onabotulinumtoxinA demonstrates similar efficacy to the standard injection technique but did not demonstrate noninferiority. Subjects preferred the reduced injection technique over the standard technique. A reduced injection technique is a safe and effective alternative to the standard technique.

Mechanisms of within-session sequential behavior in pigeons.

Correctly and efficiently selecting among options is critical to the organization of behavior across different time scales (minutes, days, seasons). As a result, understanding the mechanisms underlying the sequential behavior of animals has been a long-standing aim. In three experiments, four pigeons were tested in a four-choice simultaneous color discrimination. Across a session, they had to sequentially select a colored stimulus, and the correct color changed over four 24-trial phases (A→B→C→D). After learning this ABCD within-session sequence, tests identified that both timing and outcome feedback mechanisms contributed to the organization of pigeons' behavior. Different representational mechanisms are considered as accounts for the pigeons' observed sequential behavior.

Toxicokinetics of metformin overdose treated with CVVHDF.

A 53-year-old man died following a reported ingestion of 80 g of his metformin tablets resulting in severe, refractory shock and metformin-associated lactic acidosis. His peak serum metformin concentration was 53 µg/mL (therapeutic range 1-2 µg/mL), peak lactic acid concentration was 49.7 mmol/L, and arterial pH nadir was 7.06. He died despite vasopressors and renal replacement therapy [RRT; both intermittent hemodialysis (IHD) and continuous venovenous hemodiafiltration (CVVHDF)]. Serial metformin concentrations during CVVHDF suggested a half-life of 33-h. Similar to previous reports of RRT for metformin toxicity, CVVHDF appears to provide first-order elimination of metformin.

Open label trial of lofexidine-assisted non-opioid induction onto naltrexone extended-release injection for opioid use disorder.

Background: Opioid use disorder (OUD) continues to be major public health problem in the US and innovative medication strategies are needed. The extended-release injectable formulation of naltrexone (ER-NTX), an opioid receptor antagonist, is an effective treatment for OUD, but the need for an opioid-free period during the induction phase of treatment is a barrier to treatment success, particularly in the outpatient setting. Lofexidine, an alpha-2-adrenergic agonist, is an effective treatment for opioid withdrawal.Objectives: To evaluate the feasibility, safety, and tolerability of lofexidine for facilitating induction onto ER-NTX in the management of OUD.Methods: In an open-label, uncontrolled, 10-week outpatient clinical trial, 20 adults (four women) with OUD were treated with a fixed-flexible dosing strategy (maximum 0.54 mg 4×/daily) of lofexidine for up to 10 days to manage opioid withdrawal prior to receiving ER-NTX. The COVID-19 pandemic resulted in a modification of the study methods after enrolling 10 participants who attended all visits in person. The second group of 10 participants attended most induction period visits remotely.Results: Overall, 10 of the 20 participants (50%) achieved the primary outcome by receiving the first ER-NTX injection. Rates of induction success did not differ by the presence of fentanyl or remote visit attendance, although the small sample size provided limited statistical power. Six out of 20 participants (30%) initiated on lofexidine required dose adjustments. There were no study-related serious adverse events.Conclusions: This study provides preliminary evidence supporting the feasibility of inducting individuals with OUD onto ER-NTX using lofexidine.

Pre-neuromusculoskeletal injury Risk factor Evaluation and Post-neuromusculoskeletal injury Assessment for Return-to-duty/activity Enhancement (PREPARE) in military service members: a prospective, observational study protocol.

BACKGROUND: Non-battle related musculoskeletal injuries (MSKI) are one of the primary medical issues diminishing Service member medical readiness. The MSKI problem is challenging because it is difficult to assess all of the factors that increase MSKI risk and influence post-MSKI outcomes. Currently, there are no high-throughput, clinically-feasible, and comprehensive assessments to generate patient-centric data for informing pre- and post-MSKI risk assessment and mitigation strategies. The objective of the "Pre-neuromusculoskeletal injury Risk factor Evaluation and Post-neuromusculoskeletal injury Assessment for Return-to-duty/activity Enhancement (PREPARE)" study is to develop a comprehensive suite of clinical assessments to identify the patient-specific factors contributing to MSKI risks and undesired post-MSKI outcomes. METHODS: This is a phased approach, multi-center prospective, observational study (ClinicalTrials.gov number: NCT05111925) to identify physical and psychosocial factors contributing to greater MSKI risk and undesired post-MSKI outcomes, and to identify and validate a minimal set of assessments to personalize risk mitigation and rehabilitation strategies. In Phase I, one cohort (n = 560) will identify the physical and psychosocial factors contributing to greater MSKI risks (single assessment), while a second cohort (n = 780) will identify the post-MSKI physical and psychosocial factors contributing to undesired post-MSKI outcomes (serial assessments at enrollment, 4 weeks post-enrollment, 12 weeks post-enrollment). All participants will complete comprehensive movement assessments captured via a semi-automated markerless motion capture system and instrumented walkway, joint range of motion assessments, psychosocial measures, and self-reported physical fitness performance and MSKI history. We will follow participants for 6 months. We will identify the minimum set of clinical assessments that provide requisite data to personalize MSKI risk mitigation and rehabilitation strategies, and in Phase II validate our optimized assessments in new cohorts. DISCUSSION: The results of this investigation will provide clinically relevant data to efficiently inform MSKI risk mitigation and rehabilitation programs, thereby helping to advance medical care and retain Service members on active duty status. TRIAL REGISTRATION: PREPARE was prospectively registered on ClinicalTrials.gov (NCT05111925) on 5 NOV 2021, prior to study commencement.

e-Cigarette Use and Combustible Cigarette Smoking Initiation Among Youth: Accounting for Time-Varying Exposure and Time-Dependent Confounding.

BACKGROUND: Youth e-cigarette use is associated with the initiation of combustible cigarette smoking, but prior studies have rarely accounted for time-varying measures of e-cigarette exposure or time-dependent confounding of e-cigarette use and smoking initiation. METHODS: Using five waves of the Population Assessment of Tobacco and Health (2013-2019), we estimated marginal structural models with inverse probability of treatment and censoring weights to examine the association between time-varying e-cigarette initiation and subsequent cigarette smoking initiation among e-cigarette- and cigarette-naïve youth (12-17 years) at baseline. Time-dependent confounders used as predictors in inverse probability weights included tobacco-related attitudes or beliefs, mental health symptoms, substance use, and tobacco-marketing exposure. RESULTS: Among 9,584 youth at baseline, those who initiated e-cigarettes were 2.4 times as likely to subsequently initiate cigarette smoking as youth who did not initiate e-cigarettes (risk ratio = 2.4, 95% confidence interval [CI] = 2.1, 2.7), after accounting for time-dependent confounding and selection bias. Among youth who initiated e-cigarettes, more frequent vaping was associated with greater risk of smoking initiation (risk ratio ≥3 days/month = 1.8, 95% CI = 1.4, 2.2; 1-2 days/month = 1.2; 95% CI = 0.93, 1.6 vs. 0 days/month). Weighted marginal structural model estimates were moderately attenuated compared with unweighted estimates adjusted for baseline-only confounders. At the US population level, we estimated over half a million youth initiated cigarette smoking because of prior e-cigarette use over follow-up. CONCLUSIONS: The association between youth vaping and combustible cigarette smoking persisted after accounting for time-dependent confounding. We estimate that e-cigarette use accounts for a considerable share of cigarette initiation among US youth. See video abstract at, http://links.lww.com/EDE/B937.

Perceptual grouping and detection of trial-unique emergent structures by pigeons.

Detecting global patterns in the environment is essential to object perception and recognition. Consistent with this, pigeons have been shown to readily detect and locate geometrically arranged, structured targets embedded in randomized backgrounds. Here we show for the first time that pigeons can detect and localize trial-unique targets derived solely from global patterns resulting from periodicity, symmetry and their combination using randomly generated segments of black and white local elements. The results indicate pigeons can perceptually segment and detect a wide variety of emergent global structures and do so even when they are unique to each trial. The perceptual and cognitive mechanisms underlying this discrimination likely play important roles in the abilities of how pigeons, and likely other birds, detect and categorize the properties of natural objects at different spatial scales.

High prevalence of chronic kidney disease of unknown etiology among workers in the Mesoamerican Nephropathy Occupational Study.

BACKGROUND: Mortality from chronic kidney disease of unknown etiology (CKDu) is extremely high along the Pacific coast of Central America, particularly among sugarcane workers. The Mesoamerican Nephropathy Occupational Study (MANOS) is a prospective cohort study of CKDu among agricultural and non-agricultural workers in El Salvador and Nicaragua. The objective of this manuscript is to describe the MANOS cohort recruitment, baseline data collection, and CKDu prevalence after two rounds. METHODS: Workers with no known diabetes, hypertension, or CKD were recruited from sugarcane, corn, plantain, brickmaking, and road construction industries (n = 569). Investigators administered questionnaires, collected biological samples, and observed workers for three consecutive workdays at the worksite. Serum specimens were analyzed for kidney function parameters, and used to calculate estimated glomerular filtration rate (eGFR). At six months, serum was collected again prior to the work shift. CKD at baseline is defined as eGFR ≤ 60 ml/min/1.73m2 at both timepoints. Age-standardized prevalence was calculated by industry, country, and demographic measures. Kidney function parameters were compared by CKD status. RESULTS: Prevalence of CKD at baseline was 7.4% (n = 42). Age-standardized prevalence was highest in Salvadoran sugarcane (14.1%), followed by Salvadoran corn (11.6%), and Nicaraguan brickmaking (8.1%). Nicaraguan sugarcane had the lowest prevalence, likely due to kidney function screenings prior to employment. CONCLUSION: Despite efforts to enroll participants without CKD, our identification of prevalent CKD among agricultural and non-agricultural workers in the MANOS cohort indicates notable kidney disease in the region, particularly among sugarcane workers.

Outcomes of eosinophilic esophagitis in patients managed in a multidisciplinary clinic.

Background: Eosinophilic esophagitis is a complex disease with an increasing prevalence. Multidisciplinary teams are often needed to manage this difficult-to-treat condition. Objective: To observe the clinical and histologic outcomes of patients with eosinophilic esophagitis after management in a multidisciplinary clinic. Methods: An observational, retrospective chart review was conducted to include all patients referred to the Walter Reed National Military Medical Center multidisciplinary eosinophilic esophagitis clinic between August 2012 and February 2021. Only patients who had at least one esophagogastroduodenoscopy before referral, one or more visits and endoscopy after multidisciplinary management, and documented clinical symptoms were included. Statistical analysis was performed by using McNemar and Wilcoxon tests. Results: A total of 103 patients were included in the study, with a mean age at diagnosis of 17.9 years. Management in the multidisciplinary clinic was associated with a reduction in solid-food dysphagia by 70.9%, poor growth by 70.8%, and emesis or regurgitation by 87.5%. We observed that 48.5% and 62.1% had histologic remission (<15 eosinophils/hpf) on the initial and any post-multidisciplinary endoscopy, respectively. Only seven patients (5.8%) with two or more visits and endoscopies did not achieve histologic remission. More than two-thirds of the patients (68.9%) required combination therapy to achieve remission. Conclusion: Although an observational study, these findings may suggest that the management of patients with eosinophilic esophagitis in a multidisciplinary clinic may improve the likelihood of clinical and histologic remission. Targeted management with a multidisciplinary approach may reduce overall morbidity and slow disease progression; however, more research is needed.

Safety and tolerability of progesterone treatment for women with cocaine use disorder: a pilot treatment trial.

Background: Problematic cocaine use remains a significant public health issue, particularly among women. However, no concerted efforts have been made to target a pharmacological treatment option for women with cocaine use disorder (CUD) despite preclinical, human laboratory, and a limited number of clinical studies demonstrating that progesterone can attenuate the effects of cocaine to a greater extent in women than men.Objectives: To evaluate the safety, tolerability, and preliminary efficacy of progesterone for treating women with CUD.Methods: A 10-week double-blind randomized treatment trial was conducted. Prior to randomization, participants were required to achieve cocaine abstinence (1 week) before assignment to progesterone (up to 400 mg/day) or placebo. The primary efficacy outcomes were days to relapse and cocaine abstinence during the last 3 weeks of the trial. The frequency of side effects was also assessed.Results: 227 women were assessed for eligibility. Twenty-five women entered treatment and 21 were randomized to progesterone (n = 11) or placebo (n = 10). The majority of women relapsed in less than 4 days with no differences between the two groups. Further, there were no significant differences between the progesterone and placebo groups in terms of cocaine abstinence during the last 3 weeks of the trial (27% and 10% respectively). The most commonly reported side effects were headache and fatigue, but no group differences were noted.Conclusions: Progesterone was well tolerated and safe and supports further study is in a larger sample to determine if exogenous progesterone is an effective treatment option for women with CUD.(ClinicalTrials.gov Identifier: NCT00632099).

Longitudinal Analysis of Circulating Markers of Bone Turnover Across Multiple Decades in Osteoporotic Women.

PURPOSE: The objective of this study was to analyze changes in serum markers of bone turnover across multiple decades in osteoporotic women compared with nonosteoporotic controls, to determine their utility as potential predictors for osteoporosis. Early prediction of those at risk for osteoporosis can enable early intervention before the irreversible loss of critical bone mass. METHODS: Serum samples were obtained from 20 women given the diagnosis of osteoporosis after age 46 years and 20 age-matched women with normal bone mineral density from 4 time points in their life (ages 25-31, 32-38, 39-45, and 46-60 years). Serum levels of bone turnover markers (propeptide of type I collagen, parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin, C-terminal telopeptide of type I collagen, sclerostin, osteoprotegerin, osteopontin, and 25-OH vitamin D) were measured using commercially available arrays and kits. We used logistic regression to assess these individual serum markers as potential predictors of osteoporosis, and mixed-effects modeling to assess the change in bone turnover markers between osteoporotic and control groups over time, then performed fivefold cross-validation to assess the classification ability of the models. RESULTS: Markers of bone turnover, bone-specific alkaline phosphatase, C-terminal telopeptide of type I collagen, sclerostin, and osteocalcin were all independent predictors at multiple time points; osteopontin was an independent predictor in the 39- to 45-year age group. Receiver operating characteristic analyses demonstrated moderately strong classification ability at all time points. Sclerostin levels among groups diverged over time and were higher in the control group than the osteoporotic group, with significant differences observed at time points 3 and 4. CONCLUSIONS: Serum markers of bone turnover may be used to estimate the likelihood of osteoporosis development in individuals over time. Although prospective validation is necessary before recommending widespread clinical use, this information may be used to identify patients at risk for developing low bone mineral density long before traditional screening would ostensibly take place. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Time and Accuracy of the CEREC Omnicam Using Two Different Software Programs.

PURPOSE: The purpose of this in vitro study was to evaluate the effect of software on scan time, trueness, and precision of digital scans created using the CEREC Omnicam. MATERIAL AND METHODS: Sixty scans (20 scans/provider) of a standard reference cast were made by three different providers using the CEREC Omnicam with both CEREC Ortho 1.2.1 software (10 scans/provider) and CEREC SW 4.4.4 software (10 scans/provider). A digital full arch scan and the time to complete each scan were recorded. Trueness was calculated by overlaying the digital scans against a reference file created using the standard reference cast and a laboratory-based, white light, 3-dimensional scanner. Precision was calculated by overlaying each of digital scans against each other, using each scan as a reference. The non-parametric Mann-Whitney U-test was used to determine significant differences attributable to scanning software for each provider. RESULTS: The CEREC Ortho 1.2.1 software required a longer scan time than the CEREC SW 4.4.4 software for each provider (∼1 minute). No significant difference in trueness was observed within one provider. Two individual providers had higher precision when scanning with the CEREC Ortho 1.2.1 software than the CEREC SW 4.4.4 software. CONCLUSION: Software and scan strategy may affect the accuracy of complete-arch scans. The CEREC Ortho 1.2.1 software may demonstrate a speed-accuracy tradeoff, with generally longer scan times and possibly more precise scans.

Retentive Forces of Removable Partial Denture Clasp Assemblies Made from Polyaryletherketone and Cobalt-Chromium: A Comparative Study.

PURPOSE: To compare retentive forces of removable partial denture clasps traditionally fabricated with cobalt-chromium (CoCr) material and two computer-aided design and computer-aided manufactured (CAD/CAM) thermoplastic polymers. MATERIALS AND METHODS: Forty-eight clasp assemblies (16 CoCr, 16 polyetheretherketone (PEEK) and 16 polyetherketoneketone (PEKK) thermoplastic polymer) were fabricated for 48 mandibular tooth analogs. Individual clasps were inserted and removed on the tooth analogs utilizing a chewing simulator for 15,000 cycles to simulate 10 years of use. Retentive forces were measured utilizing a mechanical load tester at baseline and intervals of 1500 cycles. Data were analyzed with one-way Analysis of Variance, Tukey post-hoc, and paired T tests. RESULTS: Mean retentive forces between all groups were significantly different (p < 0.001). Retentive forces of CoCr clasps were significantly higher than both polymers (p < 0.001). The mean retentive forces for PEEK were not significantly different from PEKK (p = 0.23). A significant increase in retentive forces was observed for all three clasps after the first period of cycling, followed by continual decrease for the remaining cycles. At the endpoint of 15,000 cycles, no clasp assemblies showed lower retentive forces than at initial baseline. CONCLUSION: Thermoplastic polymer clasps demonstrated lower retentive forces compared to CoCr clasps. All three groups displayed a similar pattern of initial increase, followed by a gradual decrease, of retentive force. Despite this observation, the clasps maintained similar or higher retentive forces than measured at baseline. This resistance to fatigue and ability to fabricate with CAD/CAM technologies provides support for clinical use of these high-performance polymer (HPP) materials.