Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells.

CRISPR/Cas9-mediated gene editing has great potential utility for treating genetic diseases. However, its therapeutic applications are limited by unintended genomic alterations arising from DNA double-strand breaks and random integration of exogenous DNA. In this study, we propose NICER, a method for correcting heterozygous mutations that employs multiple nicks (MNs) induced by Cas9 nickase and a homologous chromosome as an endogenous repair template. Although a single nick near the mutation site rarely leads to successful gene correction, additional nicks on homologous chromosomes strongly enhance gene correction efficiency via interhomolog homologous recombination (IH-HR). This process partially depends on BRCA1 and BRCA2, suggesting the existence of several distinct pathways for MN-induced IH-HR. According to a genomic analysis, NICER rarely induces unintended genomic alterations. Furthermore, NICER restores the expression of disease-causing genes in cells derived from genetic diseases with compound heterozygous mutations. Overall, NICER provides a precise strategy for gene correction.

Efficacy of tolvaptan in an infant with syndrome of inappropriate antidiuretic hormone secretion associated with holoprosencephaly: A case report.

BACKGROUND: Holoprosencephaly (HPE) is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain. Although HPE with diabetes insipidus due to associated pituitary dysfunction has been reported, HPE with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is very rare. Tolvaptan, a vasopressin V2 receptor antagonist, is effective in adults with SIADH. However, there is no report of its efficacy in infants with SIADH. The purpose of this report is to demonstrate that tolvaptan is effective for SIADH in infants and that administration of tolvaptan eliminates the need for restriction of water intake and sodium administration. CASE SUMMARY: A 2414-g female infant was born at 38 wk by normal vaginal delivery. Facial anomalies and head magnetic resonance imaging indicated semilobar HPE. After birth, she had hyponatremia due to SIADH and was treated using water and sodium restriction. However, she developed an exaggerated response to the fluid restrictions, resulting in large fluctuations in serum sodium levels. Subsequent administration of tolvaptan improved the fluctuations in serum sodium levels without the need for adjustment of water or sodium administration. Serum sodium was maintained within the normal range after discontinuation of tolvaptan at 80 d of life. There were no side effects, such as hypernatremia or liver dysfunction, during the administration of tolvaptan. CONCLUSION: This is the first report on the safety and efficacy of tolvaptan in an infant with SIADH associated with HPE.

Outcome of extracorporeal membrane oxygenation use in severe accidental hypothermia with cardiac arrest and circulatory instability: A multicentre, prospective, observational study in Japan (ICE-CRASH study).

AIM: To elucidate the effectiveness of extracorporeal membrane oxygenation (ECMO) in accidental hypothermia (AH) patients with and without cardiac arrest (CA), including details of complications. METHODS: This study was a multicentre, prospective, observational study of AH in Japan. All adult (aged ≥18 years) AH patients with body temperature ≤32 °C who presented to the emergency department between December 2019 and March 2022 were included. Among the patients, those with CA or circulatory instability, defined as severe AH, were selected and divided into the ECMO and non-ECMO groups. We compared 28-day survival and favourable neurological outcomes at discharge between the ECMO and non-ECMO groups by adjusting for the patients' background characteristics using multivariable logistic regression analysis. RESULTS: Among the 499 patients in this study, 242 patients with severe AH were included in the analysis: 41 in the ECMO group and 201 in the non-ECMO group. Multivariable analysis showed that the ECMO group was significantly associated with better 28-day survival and favourable neurological outcomes at discharge in patients with CA compared to the non-ECMO group (odds ratio [OR] 0.17, 95% confidence interval [CI]: 0.05-0.58, and OR 0.22, 95%CI: 0.06-0.81). However, in patients without CA, ECMO not only did not improve 28-day survival and neurological outcomes, but also decreased the number of event-free days (ICU-, ventilator-, and catecholamine administration-free days) and increased the frequency of bleeding complications. CONCLUSIONS: ECMO improved survival and neurological outcomes in AH patients with CA, but not in AH patients without CA.

Hyperglycemia and Lactic Acidosis Associated with Linezolid Therapy in an Extremely Premature Infant.

The use of linezolid is relatively safe for all age categories, including premature infants. The case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid is reported. A 350-g male infant was born at 24 weeks by cesarean section. His Apgar scores were 1 and 1 at 1 and 5 min, respectively. On the day of life (DOL) 7, linezolid was started at a dose of 10 mg/kg/dose every 8 h for a catheter-related blood stream infection caused by methicillin-resistant coagulase-negative Staphylococci. After linezolid was given, serum lactate and glucose levels increased gradually. After discontinuation of linezolid on DOL 16, hyperglycemia and lactic acidosis improved immediately. In conclusion, a rare case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid was reported. It is crucial to monitor glucose levels along with lactate and pH levels during linezolid therapy.

Switching From Daily DPP-4 Inhibitor to Once-Weekly GLP-1 Receptor Activator Dulaglutide Significantly Ameliorates Glycemic Control in Subjects With Poorly Controlled Type 2 Diabetes Mellitus: A Retrospective Observational Study.

Aim: At present, daily DPP-4 inhibitors are quite frequently prescribed in subjects with type 2 diabetes mellitus (T2DM). Recently, it has been drawing much attention that once-weekly incretin-based injection dulaglutide was developed. In this study, we aimed to examine the possible effects of once-weekly GLP-1 receptor activator (GLP-1RA) dulaglutide on glycemic control as well as various metabolic parameters. Methods: We made a direct comparison between the effect of daily DPP-4 inhibitor and once-weekly dulaglutide on glycemic control in "study 1 (pre-post comparison)" and set the control group using the propensity score matching method in "study 2". Results: In study 1, switching from daily DPP-4 inhibitor to dulaglutide significantly ameliorated glycemic control in subjects with T2DM. Such effects were more obvious in poorly controlled subjects. After 1:1 propensity score matching, the switching group improved glycemic control compared with the non-switching group in study 2. Conclusion: We should bear in mind that switching from daily DPP-4 inhibitor to once-weekly GLP-1RA dulaglutide exerts more favorable effects on glycemic control regardless of age, body weight, and duration of diabetes in subjects with T2DM, especially when we fail to obtain good glycemic control with daily DPP-4 inhibitor.

Anesthetic management of a patient with severe aortic regurgitation undergoing reoperation for ascending aorta false aneurysm using hypothermia: prevention of ventricular fibrillation by nifekalant.

BACKGROUND: To prevent cardiac collapse and to protect cerebral function, hypothermic cardiopulmonary bypass is established before resternotomy. However, ventricular fibrillation under hypothermia facilitates left ventricular distension, which causes irreversible myocardial damage when the patient has aortic regurgitation. We report a case of successful management in preventing ventricular fibrillation under hypothermia by using nifekalant. CASE PRESENTATION: A 56-year-old male, who had been performed a David operation, was scheduled for a Bentall operation for a pseudo aortic aneurysm with severe aortic regurgitation. After inducing anesthesia, we administered intravenous nifekalant and a vent tube was inserted into the left ventricle under one-lung ventilation. Extracorporeal circulation was established and resternotomy started after cooling to 27 °C. Although severe bradycardia and QT prolongation were observed, ventricular fibrillation did not occur until aortic cross-clamping. CONCLUSION: Combining maintaining cerebral perfusion and avoiding left ventricle distension during hypothermia was successfully managed with nifekalant in our redo cardiac patient with aortic regurgitation.

Analysis of difficulty in placement of pulmonary artery catheter through the left internal jugular vein.

PURPOSE: The left internal jugular vein may be an alternative route for the placement of a pulmonary artery catheter when the right jugular vein is not available. Although the placement through the left internal jugular vein is expected to be more difficult, little has been written regarding difficulties in achieving proper placement of the catheter through the left internal jugular vein. METHODS: This prospective and observational study includes patients undergoing cardiac surgery with the catheter placement by monitoring the pressure waveform for 2 years. We measured the time required for the catheter to pass through the tricuspid and pulmonary valves, respectively. The data were analyzed by Mann-Whitney. P < 0.05 was considered significant. RESULTS: The catheter placement through the right and left internal jugular vein was done in 285 (group R) and 10 patients (group L), respectively. The time duration through the tricuspid valve in group L was significantly longer than that in group P (8 [5-14] s vs 70 [19.8-138] s, median [range], P < 0.01), whereas the time duration through the pulmonary valve was comparable between the two groups (15 [10-27.75] s vs 15 [10.25-19] s, median [range], P = 0.62). CONCLUSION: These results indicate that the difficulty in the catheter placement through the left jugular vein may be to pass through the tricuspid valve, not the pulmonary valve.

Effect of Combination Therapy of Canagliflozin Added to Teneligliptin Monotherapy in Japanese Subjects with Type 2 Diabetes Mellitus: A Retrospective Study.

Recently, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors have been very often used in subjects with type 2 diabetes mellitus (T2DM). In addition, combination drugs of both inhibitors have attracted much attention in aspects of its cost-effectiveness and improvement of patients' adherence. However, it is still poorly understood which factors are related to the efficacy of SGLT2 inhibitors as add-on therapy to DPP-4 inhibitors. Therefore, we aimed to elucidate in which type of individuals and/or under which conditions canagliflozin as add-on therapy to teneligliptin could exert more beneficial effects on glycemic control and/or renal protection. We retrospectively analyzed 56 Japanese subjects with T2DM in the real-world clinical practice. Three months after starting the combination therapy, the change of HbA1c (ΔHbA1c) was strongly related to HbA1c levels at baseline. As expected, serum glucagon level was increased after starting the combination therapy. Interestingly, however, the change of glucagon levels (Δglucagon) was not related to HbA1c levels at baseline, ΔHbA1c, and other parameters, which indicated that the increase of glucagon did not clinically affect the effectiveness of combination therapy. In addition, the change of urinary albumin excretion (ΔUAE) was negatively correlated with systolic blood pressure and HbA1c levels at baseline and positively correlated with the change of systolic blood pressure (ΔsBP) in univariate analysis. Furthermore, in multivariate analysis, only ΔsBP was the independent factor associated with ΔUAE. Taken together, canagliflozin as add-on therapy to teneligliptin improves glycemic control in a Δglucagon-independent manner and reduces UAE in a ΔsBP-dependent manner in Japanese subjects with T2DM.

Comparison of HbA1c levels and body mass index for prevention of diabetic kidney disease: A retrospective longitudinal study using outpatient clinical data in Japanese patients with type 2 diabetes mellitus.

AIM: This study examined the association among the onset of diabetic kidney disease (DKD), blood glucose levels (HbA1C), and body mass index (BMI) in Japanese patients with type 2 diabetes mellitus. METHODS: Patients eligible for this study included those with type 2 diabetes who visited the outpatient clinic at Kawasaki Medical School Hospital between 2000 and 2018 and were followed up for more than two years. The Cox proportional hazards model was used in four categories of subjects: at the beginning of the follow-up period, "controlled" or "uncontrolled" glycemic control based on HbA1c and "overweight" or "non-overweight" based on BMI. RESULTS: After dividing the participants into four categories according to HbA1c (lower than 7.0% (C) or higher (U)), and BMI (25 kg/m2 or higher (O) or lower (N)), hazard ratios for groups CO, UN, and UO were 1.40 (95% CI 1.03-1.90, P = 0.030), 1.40 (1.04-1.88, P = 0.027), and 1.54 (1.12-2.11, P = 0.008), respectively, compared with the CN reference group, after adjustment was made for age, sex, duration of diabetes, and medication for hypertension or dyslipidemia. CONCLUSION: Maintenance of both an HbA1c level lower than 7.0% and a BMI lower than 25 kg/m2 was important for the prevention of DKD in Japanese patients with type 2 diabetes mellitus. Both factors had a similar effect on DKD in this study.

Delayed diagnosis of traumatic ventricular septal perforation in penetrating chest injury: hematoma formation in the ventricular septum in CT suggests perforation.

BACKGROUND: Ventricular septal perforation (VSP) can be caused by a penetrating cardiac injury. Diagnosis of VSP tends to be delayed because a shunt might not be detected by color flow Doppler at an early stage following injury. CASE PRESENTATION: A 60-year-old man with depression was admitted to the emergency center after a knife injury in the chest. A focused assessment with sonography for trauma revealed cardiac tamponade. Shortly after an open cardiac massage and a pericardiotomy, his spontaneous circulation returned. At a later stage, follow-up computed tomography, echocardiography, and left ventriculography showed traumatic ventricular septal perforation. Conservative therapy was chosen because the pulmonary blood flow/systemic blood flow ratio was 1.42. CONCLUSION: The initial contrast computed tomography shows a septal hematoma. Its presence could be perceived as a perforation site in the interventricular septum.

Eicosapentaenoic acid/arachidonic acid ratio and weight loss during hospitalization for glycemic control among overweight Japanese patients with type 2 diabetes: a retrospective observational study.

BACKGROUND: The study aimed to examine the relationship between levels of serum eicosapentaenoic acid (EPA), arachidonic acid (AA), as well as EPA/AA ratio and weight loss during hospitalization in participants considered to be overweight, with type 2 diabetes. METHODS: The study participants included 142 patients who were hospitalized for treatment of type 2 diabetes. We divided the participants into two groups depending on the achievenemt in reduction of bodyweight 3% or more during hospitalization and examined the relationship between serum levels of EPA and AA, as well as ratio of EPA/AA on admission and effectiveness of weight loss under strict dietary therapy during hospitalization, using Cox proportional hazard models. RESULTS: After adjustment was made for several confounders, the hazard ratio of effective weight loss for logarithmical serum EPA was 1.59 (95% CI 1.02-2.49, P = 0.04) and for logarithmical EPA/AA ratio 1.64 (1.03-2.61, P = 0.04), whereas the hazard ratio for effective weight loss for logarithmical serum AA was 1.11 (0.45-2.78, P = 0.82). In addition, after dividing EPA/AA ratio and serum EPA into quartiles based on participant number, the hazard ratio for the highest quartile of EPA/AA ratio was 2.33 (1.14-4.77, P = 0.02), and for the highest quartile of serum EPA 1.60 (0.80-3.19, P = 0.18) compared with the lowest quartile. CONCLUSION: These results suggest the possibility that EPA is involved in bodyweight change under a caloric-restriction regimen. In addition, EPA/AA ratio was found to be a better predictor of medical intervention for weight loss among overweight patients with type 2 diabetes, compared with serum EPA level.

Cortical and Subcortical Projections from Granular Insular Cortex Receiving Orofacial Proprioception.

We have recently revealed that the proprioceptive signal from jaw-closing muscle spindles (JCMSs) is conveyed to the dorsal part of granular insular cortex rostroventrally adjacent to the rostralmost part of secondary somatosensory cortex (dGIrvs2) via the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM) in rats. However, it remains unclear to which cortical or subcortical structures the JCMS proprioceptive information is subsequently conveyed from the dGIrvs2. To test this issue, we injected an anterograde tracer, biotinylated dextranamine, into the electophysiologically identified dGIrvs2, and analyzed the resultant distribution profiles of labeled axon terminals in rats. Labeled terminals were distributed with an ipsilateral predominance. In the cerebral cortex, they were seen in the primary and secondary somatosensory cortices, lateral and medial agranular cortices and dorsolateral orbital cortex. In the basal ganglia, they were found in the caudate putamen, core part of accumbens nucleus, lateral globus pallidus, subthalamic nucleus, and substantia nigra pars compacta and pars reticulata. They were also observed in the central amygdaloid nucleus and extended amygdala (the interstitial nucleus of posterior limb of anterior commissure and the juxtacapsular part of lateral division of bed nucleus of stria terminalis). In the thalamus, they were seen in the reticular nucleus, ventromedial nucleus, core VPM, parvicellular part of ventral posterior nucleus, oval paracentral nucleus, medial and triangular parts of posterior nucleus, and zona incerta as well as the VPMcvm. These data suggest that the JCMS proprioceptive information through the dGIrvs2 is transmitted to the emotional 'limbic' regions as well as sensorimotor regions.

Survey of Denture Repair Cases: Denture Reinforcement Makes Patients Able to Use Their Dentures for Longer Periods.

PURPOSE: To evaluate the long-term effects of preventive measures against denture fracture using clinical surveys of denture fracture cases from 1984 and 2009. MATERIALS AND METHODS: This study included 128 patients who presented with a chief complaint of denture fracture and received denture repair treatment in 2009. The following data were collected: denture repair procedure; location of denture base fracture (with or without reinforcement); and period of denture use from insertion to repair. Significant differences in characteristics between patients treated in 1984 and 2009 were determined using the chi-square test (P < .05). RESULTS: In 2009, denture fractures comprised 55.5% of all repair cases. The most frequent location of denture fracture was around the clasp and metal in the denture base. Approximately 45% of all dentures were reinforced. The mean period from denture insertion to repair was 37 months. The number of denture fractures significantly decreased between 1984 and 2009 (P < .05), and the number of dentures with reinforcement significantly increased (P < .05). The mean period from denture insertion to repair also increased. CONCLUSION: These findings suggest that denture reinforcement as a preventive measure is effective against denture fracture, allowing patients to use their dentures more effectively.

Effect of Attachment Type on Implant Strain in Maxillary Implant Overdentures: Comparison of Ball, Locator, and Magnet Attachments. Part 2: Palateless Dentures.

PURPOSE: Palateless maxillary implant overdentures are often used for patients experiencing problems with a full-palate denture. However, palateless overdentures are reported to be a risk factor for implant complications. The purpose of this study was to examine the strain on implants beneath palateless overdentures with unsplinted attachments under various implant distributions. MATERIALS AND METHODS: A maxillary edentulous model with implants and an experimental palateless overdenture were fabricated. Four strain gauges were attached to each implant, positioned in the anterior, premolar, and molar areas. Three types of unsplinted attachments (ball, locator, and magnet) were set on the implants under various implant distributions. A vertical occlusal load of 98 N was applied through the mandibular complete denture, and the bending strain on the implants was compared using the Kruskal-Wallis test (P = .05). RESULTS: When comparing the strain among different attachments, those using a magnet attachment were the smallest and those using a ball attachment were the greatest, and this difference was significant in most situations (P < .05). When comparing the strain among different implant distributions, the strain on a four-implant distribution was significantly smaller than that on a two-implant distribution in most situations (P < .05), and those using premolar and molar implants recorded the smallest strain. The strain on implants using a locator attachment tended to be midway between those using ball and magnet attachments, regardless of the implant distribution. CONCLUSION: In most implant distributions, magnet attachments decrease the strain on implants more than ball and locator attachments. The most favorable unsplinted attachments for use beneath palateless overdentures to decrease the implant strain are magnet attachments and four implants placed in the premolar and molar areas.

Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168.

The E3 ubiquitin (Ub) ligase RNF168 plays a critical role in the initiation of the DNA damage response to double-strand breaks (DSBs). The recruitment of RNF168 by ubiquitylated targets involves two distinct regions, Ub-dependent DSB recruitment module (UDM) 1 and UDM2. Here we report the crystal structures of the complex between UDM1 and Lys63-linked diUb (K63-Ub2) and that between the C-terminally truncated UDM2 (UDM2ΔC) and K63-Ub2. In both structures, UDM1 and UDM2ΔC fold as a single α-helix. Their simultaneous bindings to the distal and proximal Ub moieties provide specificity for Lys63-linked Ub chains. Structural and biochemical analyses of UDM1 elucidate an Ub-binding mechanism between UDM1 and polyubiquitylated targets. Mutations of Ub-interacting residues in UDM2 prevent the accumulation of RNF168 to DSB sites in U2OS cells, whereas those in UDM1 have little effect, suggesting that the interaction of UDM2 with ubiquitylated and polyubiquitylated targets mainly contributes to the RNF168 recruitment.

Precise and efficient nucleotide substitution near genomic nick via noncanonical homology-directed repair.

CRISPR/Cas9, which generates DNA double-strand breaks (DSBs) at target loci, is a powerful tool for editing genomes when codelivered with a donor DNA template. However, DSBs, which are the most deleterious type of DNA damage, often result in unintended nucleotide insertions/deletions (indels) via mutagenic nonhomologous end joining. We developed a strategy for precise gene editing that does not generate DSBs. We show that a combination of single nicks in the target gene and donor plasmid (SNGD) using Cas9D10A nickase promotes efficient nucleotide substitution by gene editing. Nicking the target gene alone did not facilitate efficient gene editing. However, an additional nick in the donor plasmid backbone markedly improved the gene-editing efficiency. SNGD-mediated gene editing led to a markedly lower indel frequency than that by the DSB-mediated approach. We also show that SNGD promotes gene editing at endogenous loci in human cells. Mechanistically, SNGD-mediated gene editing requires long-sequence homology between the target gene and repair template, but does not require CtIP, RAD51, or RAD52. Thus, it is considered that noncanonical homology-directed repair regulates the SNGD-mediated gene editing. In summary, SNGD promotes precise and efficient gene editing and may be a promising strategy for the development of a novel gene therapy approach.

Abiotic Stress Phenotypes Are Associated with Conserved Genes Derived from Transposable Elements.

Plant phenomics offers unique opportunities to accelerate our understanding of gene function and plant response to different environments, and may be particularly useful for studying previously uncharacterized genes. One important type of poorly characterized genes is those derived from transposable elements (TEs), which have departed from a mobility-driven lifestyle to attain new adaptive roles for the host (exapted TEs). We used phenomics approaches, coupled with reverse genetics, to analyze T-DNA insertion mutants of both previously reported and novel protein-coding exapted TEs in the model plant Arabidopsis thaliana. We show that mutations in most of these exapted TEs result in phenotypes, particularly when challenged by abiotic stress. We built statistical multi-dimensional phenotypic profiles and compared them to wild-type and known stress responsive mutant lines for each particular stress condition. We found that these exapted TEs may play roles in responses to phosphate limitation, tolerance to high salt concentration, freezing temperatures, and arsenic toxicity. These results not only experimentally validate a large set of putative functional exapted TEs recently discovered through computational analysis, but also uncover additional novel phenotypes for previously well-characterized exapted TEs in A. thaliana.

Thalamo-insular pathway conveying orofacial muscle proprioception in the rat.

Little is known about how proprioceptive signals arising from muscles reach to higher brain regions such as the cerebral cortex. We have recently shown that a particular thalamic region, the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM), receives the proprioceptive signals from jaw-closing muscle spindles (JCMSs) in rats. In this study, we further addressed how the orofacial thalamic inputs from the JCMSs were transmitted from the thalamus (VPMcvm) to the cerebral cortex in rats. Injections of a retrograde and anterograde neuronal tracer, wheat-germ agglutinin-conjugated horseradish peroxidase (WGA-HRP), into the VPMcvm demonstrated that the thalamic pathway terminated mainly in a rostrocaudally narrow area in the dorsal part of granular insular cortex rostroventrally adjacent to the rostralmost part of the secondary somatosensory cortex (dGIrvs2). We also electrophysiologically confirmed that the dGIrvs2 received the proprioceptive inputs from JCMSs. To support the anatomical evidence of the VPMcvm-dGIrvs2 pathway, injections of a retrograde neuronal tracer Fluorogold into the dGIrvs2 demonstrated that the thalamic neurons projecting to the dGIrvs2 were confined in the VPMcvm and the parvicellular part of ventral posterior nucleus. In contrast, WGA-HRP injections into the lingual nerve area of core VPM demonstrated that axon terminals were mainly labeled in the core regions of the primary and secondary somatosensory cortices, which were far from the dGIrvs2. These results suggest that the dGIrvs2 is a specialized cortical region receiving the orofacial proprioceptive inputs. Functional contribution of the revealed JCMSs-VPMcvm-dGIrvs2 pathway to Tourette syndrome is also discussed.

Influence of Abutment Angle on Implant Strain When Supporting a Distal Extension Removable Partial Dental Prosthesis: An In Vitro Study.

PURPOSE: This study evaluated the impact of angled abutments on strain in implants supporting a distal extension removable partial denture. MATERIALS AND METHODS: An in vitro model of an implant supporting a distal extension removable partial denture was developed. The implant was positioned with a 17- or 30-degree mesial inclination, with either a healing abutment or a corrective multiunit abutment. Levels of strain under load were compared, and the results were compared using t test (P = .05). RESULTS: Correcting angulation with a multiunit angled abutment significantly decreased strain (P < .05) when compared with a healing abutment. CONCLUSION: An angled abutment decreased the strain on an inclined implant significantly more than a healing abutment when loaded under a distal extension removable partial denture.

Root Fracture of Abutment Teeth for Partial Removable Dental Prostheses.

PURPOSE: Root fracture is a common and serious cause of abutment tooth loss. No studies to date have comprehensively assessed the individual contributions of the factors that increase stress on abutment teeth. The purpose of this study was to analyze the stress distribution in abutment teeth based on a three-dimensional finite element model and to analyze the factors that affect stress distribution. MATERIALS AND METHODS: Models were generated from the computed tomography data of a single patient, consisting of a mandibular second premolar abutment tooth, bone, residual mucous membrane, and a partial removable dental prosthesis (PRDP). Four models were prepared using different types of endodontic posts and cores. Akers clasps were used for the simulated PRDPs, and a vertical load was applied to the occlusal surface of the PRDPs. Debonding between the post and root was simulated. The Young modulus of the residual ridge was reduced to simulate a poor fit between the denture base and the residual ridge. Stress distribution in the abutment tooth root was observed, and the maximum principal stress was evaluated. RESULTS: The nonmetal post model and the mesial rest model reduced stress concentration in the root. The stress increased in models simulating debonding and poor fit. The results of the multiple linear regression analysis confirmed that debonding and poor fit were significantly associated with root stress. CONCLUSION: Within the limitations of this study, it is suggested that the bonding integrity of posts and adequate fit of the denture base are important factors affecting the longevity of abutment teeth for PRDPs.