EPAC1 inhibition protects the heart from doxorubicin-induced toxicity.

Anthracyclines, such as doxorubicin (Dox), are widely used chemotherapeutic agents for the treatment of solid tumors and hematologic malignancies. However, they frequently induce cardiotoxicity leading to dilated cardiomyopathy and heart failure. This study sought to investigate the role of the exchange protein directly activated by cAMP (EPAC) in Dox-induced cardiotoxicity and the potential cardioprotective effects of EPAC inhibition. We show that Dox induces DNA damage and cardiomyocyte cell death with apoptotic features. Dox also led to an increase in both cAMP concentration and EPAC1 activity. The pharmacological inhibition of EPAC1 (with CE3F4) but not EPAC2 alleviated the whole Dox-induced pattern of alterations. When administered in vivo, Dox-treated WT mice developed a dilated cardiomyopathy which was totally prevented in EPAC1 knock-out (KO) mice. Moreover, EPAC1 inhibition potentiated Dox-induced cell death in several human cancer cell lines. Thus, EPAC1 inhibition appears as a potential therapeutic strategy to limit Dox-induced cardiomyopathy without interfering with its antitumoral activity.

Preoperative visualization of the lingual nerve by 3D double-echo steady-state MRI in surgical third molar extraction treatment.

OBJECTIVES: To assess the lingual nerve (LN) visualization using a 3D double-echo steady-state MRI sequence (3D-DESS). MATERIALS AND METHODS: Three readers prospectively evaluated the LN for its continuous visibility in 3D-DESS MRI in 19 patients with an indication for removal of mandibular impacted third molars, using a 5-point scale (4 = excellent to 0 = none). Six LN anatomical intermediate points (IP) were selected and checked for their detectability by a 4-point scale (4 = yes to1 = no). Inter- and intra-rater agreement was evaluated using intraclass correlation coefficient and percentage of agreement. RESULTS: The average nerve continuity score was 3.3 ± 0.46. In 35% of the cases, the entire course was continuously visible. In 10%, the proximal and 60%, the distal part of the nerve was not continuously visible. Inter- and intra-reader agreement was good (ICC = 0.76, ICC = 0.75). The average detectability score of all IP was 3.7 ± 0.41. From IP1 to IP5, the detectability was excellent; meanwhile, IP6 had lower visibility. The inter- and intra-reader percentage of agreement was 77% and 87%. CONCLUSIONS: The 3D-DESS sequence allowed accurate and continuous visualization of the LN with high reproducibility in more than one-third of the patients. This could improve the preoperative clarification of the LN position and thereby reduce complications during dentoalveolar surgical interventions. CLINICAL RELEVANCE: 3D-DESS MRI might be beneficial in clinical scenarios where the second molar is elongated or presents a difficult rotational position while simultaneously having a close positional relationship to the third molar. Thereby, osteotomy performed more lingually, indicating extended lingual flap detachment may increase the risk of LN damage.

Spatiotemporal AMPKα2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only.

BACKGROUND: The AMP-activated protein kinase (AMPK) is a major regulator of cellular energetics which plays key role in acute metabolic response and in long-term adaptation to stress. Recent works have also suggested non-metabolic effects. METHODS: To decipher AMPK roles in the heart, we generated a cardio-specific inducible model of gene deletion of the main cardiac catalytic subunit of AMPK (Ampkα2) in mice. This allowed us to avoid the eventual impact of AMPK-KO in peripheral organs. RESULTS: Cardio-specific Ampkα2 deficiency led to a progressive left ventricular systolic dysfunction and the development of cardiac fibrosis in males. We observed a reduction in complex I-driven respiration without change in mitochondrial mass or in vitro complex I activity, associated with a rearrangement of the cardiolipins and reduced integration of complex I into the electron transport chain supercomplexes. Strikingly, none of these defects were present in females. Interestingly, suppression of estradiol signaling by ovariectomy partially mimicked the male sensitivity to AMPK loss, notably the cardiac fibrosis and the rearrangement of cardiolipins, but not the cardiac function that remained protected. CONCLUSION: Our results confirm the close link between AMPK and cardiac mitochondrial function, but also highlight links with cardiac fibrosis. Importantly, we show that AMPK is differently involved in these processes in males and females, which may have clinical implications for the use of AMPK activators in the treatment of heart failure.

Involvement of CFTR in the pathogenesis of pulmonary arterial hypertension.

INTRODUCTION: A reduction in pulmonary artery relaxation is a key event in the pathogenesis of pulmonary arterial hypertension (PAH). Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in airway epithelial cells plays a central role in cystic fibrosis; CFTR is also expressed in pulmonary arteries and has been shown to control endothelium-independent relaxation. AIM AND OBJECTIVES: We aimed to delineate the role of CFTR in PAH pathogenesis through observational and interventional experiments in human tissues and animal models. METHODS AND RESULTS: Reverse-transcriptase quantitative PCR, confocal imaging and electron microscopy showed that CFTR expression was reduced in pulmonary arteries from patients with idiopathic PAH (iPAH) and in rats with monocrotaline-induced pulmonary hypertension (PH). Moreover, using myography on human, pig and rat pulmonary arteries, we demonstrated that CFTR activation induces pulmonary artery relaxation. CFTR-mediated pulmonary artery relaxation was reduced in pulmonary arteries from iPAH patients and rats with monocrotaline- or chronic hypoxia-induced PH. Long-term in vivo CFTR inhibition in rats significantly increased right ventricular systolic pressure, which was related to exaggerated pulmonary vascular cell proliferation in situ and vessel neomuscularisation. Pathologic assessment of lungs from patients with severe cystic fibrosis (F508del-CFTR) revealed severe pulmonary artery remodelling with intimal fibrosis and medial hypertrophy. Lungs from homozygous F508delCftr rats exhibited pulmonary vessel neomuscularisation. The elevations in right ventricular systolic pressure and end diastolic pressure in monocrotaline-exposed rats with chronic CFTR inhibition were more prominent than those in vehicle-exposed rats. CONCLUSIONS: CFTR expression is strongly decreased in pulmonary artery smooth muscle and endothelial cells in human and animal models of PH. CFTR inhibition increases vascular cell proliferation and strongly reduces pulmonary artery relaxation.

Accuracy of guided biopsy of the jawbone in a clinical setting: A retrospective analysis.

The aim of this study was to investigate the accuracy of a previously described technique for guided biopsy of osseous pathologies of the jawbone in a clinical setting. The data sets of patients who had undergone guided biopsy procedures were retrospectively examined for accuracy. Digital planning of the biopsies and manufacturing of the tooth-supported drilling template were performed with superimposed cone beam computed tomography and intraoral scans using implant planning software. After a trephine biopsy was taken using the template, the postoperative low-dose cone beam computed tomography was analyzed for accuracy using the planning software with the corresponding (digitally-planned) biopsy cylinder. The mean angular deviation was 4.35 ± 2.5°. The mean depth deviation was -1.40 ± 1.41 mm. Guided biopsy seems to be an alternative to a conventional approach for minimally invasive and highly accurate jawbone biopsy.

Kcnk3 dysfunction exaggerates the development of pulmonary hypertension induced by left ventricular pressure overload.

AIMS: Pulmonary hypertension (PH) is a common complication of left heart disease (LHD, Group 2 PH) leading to right ventricular (RV) failure and death. Several loss-of-function (LOF) mutations in KCNK3 were identified in pulmonary arterial hypertension (PAH, Group 1 PH). Additionally, we found that KCNK3 dysfunction is a hallmark of PAH at pulmonary vascular and RV levels. However, the role of KCNK3 in the pathobiology of PH due to LHD is unknown. METHODS AND RESULTS: We evaluated the role of KCNK3 on PH induced by ascending aortic constriction (AAC), in WT and Kcnk3-LOF-mutated rats, by echocardiography, RV catheterization, histology analyses, and molecular biology experiments. We found that Kcnk3-LOF-mutation had no consequence on the development of left ventricular (LV) compensated concentric hypertrophy in AAC, while left atrial emptying fraction was impaired in AAC-Kcnk3-mutated rats. AAC-animals (WT and Kcnk3-mutated rats) developed PH secondary to AAC and Kcnk3-mutated rats developed more severe PH than WT. AAC-Kcnk3-mutated rats developed RV and LV fibrosis in association with an increase of Col1a1 mRNA in right ventricle and left ventricle. AAC-Kcnk3-mutated rats developed severe pulmonary vascular (pulmonary artery as well as pulmonary veins) remodelling with intense peri-vascular and peri-bronchial inflammation, perivascular oedema, alveolar wall thickening, and exaggerated lung vascular cell proliferation compared to AAC-WT-rats. Finally, in lung, right ventricle, left ventricle, and left atrium of AAC-Kcnk3-mutated rats, we found a strong increased expression of Il-6 and periostin expression and a reduction of lung Ctnnd1 mRNA (coding for p120 catenin), contributing to the exaggerated pulmonary and heart remodelling and pulmonary vascular oedema in AAC-Kcnk3-mutated rats. CONCLUSIONS: Our results indicate that Kcnk3-LOF is a key event in the pathobiology of PH due to AAC, suggesting that Kcnk3 channel dysfunction could play a potential key role in the development of PH due to LHD.

Cell seeding accelerates the vascularization of tissue engineering constructs in hypertensive mice.

Rapid blood vessel ingrowth into transplanted constructs represents the key requirement for successful tissue engineering. Seeding three-dimensional scaffolds with suitable cells is an approved technique for this challenge. Since a plethora of patients suffer from widespread diseases that limit the capacity of neoangiogenesis (e.g., hypertension), we investigated the incorporation of cell-seeded poly-L-lactide-co-glycolide scaffolds in hypertensive (BPH/2J, group A) and nonhypertensive (BPN/3J, group B) mice. Collagen-coated scaffolds (A1 and B1) were additionally seeded with osteoblast-like (A2 and B2) and mesenchymal stem cells (A3 and B3). After implantation into dorsal skinfold chambers, inflammation and newly formed microvessels were measured using repetitive intravital fluorescence microscopy for 2 weeks. Apart from a weak inflammatory response in all groups, significantly increased microvascular densities were found in cell-seeded scaffolds (day 14, A2: 192 ± 12 cm/cm2, A3: 194 ± 10 cm/cm2, B2: 249 ± 19 cm/cm2, B3: 264 ± 17 cm/cm2) when compared with controls (A1: 129 ± 10 cm/cm2, B1: 185 ± 8 cm/cm2). In this context, hypertensive mice showed reduced neoangiogenesis in comparison with nonhypertensive animals. Therefore, seeding approved scaffolds with organ-specific or pluripotent cells is a very promising technique for tissue engineering in hypertensive organisms.

Trichloroethylene increases pulmonary endothelial permeability: implication for pulmonary veno-occlusive disease.

Trichloroethylene exposure is a major risk factor for pulmonary veno-occlusive disease. We demonstrated that trichloroethylene alters the endothelial barrier integrity, at least in part, through vascular endothelial (VE)-Cadherin internalisation, and suggested that this mechanism may play a role in the development of pulmonary veno-occlusive disease.

Autogenous bone augmentation from the zygomatic alveolar crest: a volumetric retrospective analysis in the maxilla.

BACKGROUND: Autogenous bone augmentation is the gold standard for the treatment of extended bone defects prior to implantation. Bone augmentation from the zygomatic crest is a valuable option with several advantages, but the current literature for this treatment is scant. The aim of this study was to evaluate the increase in bone volume after locoregional bone augmentation using autogenous bone from the zygomatic alveolar crest as well as the complications and success rate. RESULTS: Analysis of the augmented bone volume in seven patients showed a maximum volume gain of 0.97 cm3. An average of 0.54 cm3 of autogenous bone (SD 0.24 cm3; median: 0.54 cm3) was augmented. Implantation following bone augmentation was possible in all cases. Complications occurred in three patients. CONCLUSION: The zygomatic alveolar crest is a valuable donor site for autogenous alveolar onlay grafting in a locoregional area such as the maxillary front. Low donor site morbidity, good access, and its suitable convexity make it a beneficial choice for autogenous bone augmentation.

Antimicrobial peptide gene expression in medication-related osteonecrosis of the jaw.

Bisphosphonates and denosumab are commonly used antiresorptive therapies in patients with bone metastasis and osteoporosis. Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of these drugs, and infection has been recognized as a contributing factor. Current therapeutic options for MRONJ show limited effectiveness, therefore necessitating novel treatment strategies. Bisphosphonates have recently been reported to induce the expression of antimicrobial peptides (AMPs), an inherent component of the immune system. Therefore, the aim of the present study was to investigate and compare the influence of the anti-RANKL antibody denosumab and bisphosphonates on the gene expression of selected AMPs: human α-defensin-1, human α-defensin-3, human ß-defensin-1, and human ß-defensin-3. Bone specimens were collected from patients with MRONJ who had been treated with bisphosphonates (n = 6) or denosumab (n = 6), and from healthy subjects (n = 6) with no history of treatment with bone metabolism-influencing drugs. Reverse transcription-quantitative polymerase chain reaction was used to quantify the expression levels of selected AMPs. Samples from patients treated with denosumab showed significantly higher mRNA expression of human α-defensin-3 and human ß-defensin-3 than those from healthy subjects. This finding is similar to previously described upregulated expression of human defensins in patients with MRONJ after bisphosphonates treatment. This suggests that the elevated expression of defensins may be at least a part of the mechanism underlying the pathogenesis of osteonecrosis induced by antiresorptive therapies, which can serve as a new target for potential treatment of MRONJ.

Microtubule polymerization state and clathrin-dependent internalization regulate dynamics of cardiac potassium channel: Microtubule and clathrin control of KV1.5 channel.

Ion channel trafficking powerfully influences cardiac electrical activity as it regulates the number of available channels at the plasma membrane. Studies have largely focused on identifying the molecular determinants of the trafficking of the atria-specific KV1.5 channel, the molecular basis of the ultra-rapid delayed rectifier current IKur. Besides, regulated KV1.5 channel recycling upon changes in homeostatic state and mechanical constraints in native cardiomyocytes has been well documented. Here, using cutting-edge imaging in live myocytes, we investigated the dynamics of this channel in the plasma membrane. We demonstrate that the clathrin pathway is a major regulator of the functional expression of KV1.5 channels in atrial myocytes, with the microtubule network as the prominent organizer of KV1.5 transport within the membrane. Both clathrin blockade and microtubule disruption result in channel clusterization with reduced membrane mobility and internalization, whereas disassembly of the actin cytoskeleton does not. Mobile KV1.5 channels are associated with the microtubule plus-end tracking protein EB1 whereas static KV1.5 clusters are associated with stable acetylated microtubules. In human biopsies from patients in atrial fibrillation associated with atrial remodeling, drastic modifications in the trafficking balance occurs together with alteration in microtubule polymerization state resulting in modest reduced endocytosis and increased recycling. Consequently, hallmark of atrial KV1.5 dynamics within the membrane is clathrin- and microtubule- dependent. During atrial remodeling, predominance of anterograde trafficking activity over retrograde trafficking could result in accumulation ok KV1.5 channels in the plasma membrane.

Radiologic Analysis of Surgically Treated Fractures of the Condylar Process by an Endoscopic-Assisted Transoral Approach.

PURPOSE: This study analyzed the radiologic outcomes of patients with unilateral mandibular condylar fractures treated with open reduction-internal fixation (ORIF) through a transoral approach. PATIENTS AND METHODS: In this retrospective study, the radiologic images of 40 patients who underwent open reduction-internal fixation through a transoral approach were presented to 2 independent examiners. All patients underwent the surgical procedure between January 2015 and December 2016 at the Department of Cranio-Maxillofacial Surgery at UniversitätsSpital Zürich and were included in a previous functional outcome study. The surgical results were analyzed and graded as poor, acceptable, or good. The examiners declared whether they would have made any intraoperative revisions if the radiologic information had been available. Finally, the examiners estimated the required duration of elastic intermaxillary fixation (IMF) from the radiologic images, which was compared with the actual duration. RESULTS: Fracture reduction was classified as good in 33 cases (82.5%), acceptable in 5 cases, and poor in 2 cases by one examiner and as good in 32 cases (80%), acceptable in 6 cases, and poor in 2 cases by the other examiner. The inter-rater reliability was determined to be good (Cohen κ = 0.92). Correct osteosynthesis placement was found in 19 cases by one examiner and in 21 cases by the other examiner, with good inter-rater reliability (κ = 0.8). Moderate inter-rater reliability (κ = 0.4) was found for the required duration of elastic IMF. Furthermore, the estimated elastic IMF duration matched the actual duration in fewer than half of the cases. CONCLUSIONS: It is feasible to achieve reliably good radiologic results when operating on condylar process fractures by a transoral approach with endoscopic assistance and angled instruments. Intraoperative 3-dimensional imaging enables instant quality control and prompts surgical revision if needed.

Use of a xenogeneic collagen matrix on extraction sockets: a new approach in ARONJ prevention (in german) / Plastische Deckung von Extraktionsalveolen mit einem xenogenen Bindegewebstransplantat

Antiresorptive drugs are increasingly used for the treatment of osteoporosis, various bone pathologies and malignant tumors. Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a relevant complication, especially in nonhealing extraction sockets. Prescription of antibiotics in combination with a safely guaranteed closure of the extraction socket is considerably reducing the risk of ARONJ development. Full mucosal coverage usually requires the formation of a full thickness flap, which involves periosteal disclosure of the remodeled bone. In this new approach, primary wound closure is performed by covering the extraction socket with a xenogeneic collagen matrix. Ultimately, elevation of a periosteal flap and additional exposure of the surrounding alveolar bone is avoidable. The technique is exemplified on a patient case with a perennial anti resorptive medication history.

Orai1 Channel Inhibition Preserves Left Ventricular Systolic Function and Normal Ca2+ Handling After Pressure Overload.

BACKGROUND: Orai1 is a critical ion channel subunit, best recognized as a mediator of store-operated Ca2+ entry (SOCE) in nonexcitable cells. SOCE has recently emerged as a key contributor of cardiac hypertrophy and heart failure but the relevance of Orai1 is still unclear. METHODS: To test the role of these Orai1 channels in the cardiac pathophysiology, a transgenic mouse was generated with cardiomyocyte-specific expression of an ion pore-disruptive Orai1R91W mutant (C-dnO1). Synthetic chemistry and channel screening strategies were used to develop 4-(2,5-dimethoxyphenyl)-N-[(pyridin-4-yl)methyl]aniline (hereafter referred to as JPIII), a small-molecule Orai1 channel inhibitor suitable for in vivo delivery. RESULTS: Adult mice subjected to transverse aortic constriction (TAC) developed cardiac hypertrophy and reduced ventricular function associated with increased Orai1 expression and Orai1-dependent SOCE (assessed by Mn2+ influx). C-dnO1 mice displayed normal cardiac electromechanical function and cellular excitation-contraction coupling despite reduced Orai1-dependent SOCE. Five weeks after TAC, C-dnO1 mice were protected from systolic dysfunction (assessed by preserved left ventricular fractional shortening and ejection fraction) even if increased cardiac mass and prohypertrophic markers induction were observed. This is correlated with a protection from TAC-induced cellular Ca2+ signaling alterations (increased SOCE, decreased [Ca2+]i transients amplitude and decay rate, lower SR Ca2+ load and depressed cellular contractility) and SERCA2a downregulation in ventricular cardiomyocytes from C-dnO1 mice, associated with blunted Pyk2 signaling. There was also less fibrosis in heart sections from C-dnO1 mice after TAC. Moreover, 3 weeks treatment with JPIII following 5 weeks of TAC confirmed the translational relevance of an Orai1 inhibition strategy during hypertrophic insult. CONCLUSIONS: The findings suggest a key role of cardiac Orai1 channels and the potential for Orai1 channel inhibitors as inotropic therapies for maintaining contractility reserve after hypertrophic stress.

A volumetric assessment and follow-up of a granuloma gravidarum in the anterior maxilla.

AIM: Granuloma gravidarum (GG) is a benign lesion of the soft tissue. The aim of this technical note is the volumetric assessment and follow-up 3D measurement of a GG in the anterior maxilla. MATERIALS AND METHODS: A 35-year-old female patient who was 7 months pregnant was referred due to a soft tissue tumor in the papilla of tooth 21. A biopsy verified a pyogenic granuloma gravidarum. Initial and consecutive volumeatric measurements were made with an intraoral scanner during the patient's pregnancy and until 16 months postpartum. RESULTS: The volumetric assessment showed a continuous growth of the tumor and a consecutive volume reduction 16 months postpartum. In comparison with the level of the papilla of the contralateral incisor, there was an almost complete remission at the last follow-up. CONCLUSION: Intraoral scans can serve for the volumetric assessment of soft tissue tumors of the alveolar crest. Image superimposition enables the quantification of changes in morphology. This supports clinical follow-ups and enables the quantification of clinical observations.

Associated Ophthalmic Injuries in Patients With Fractures of the Midface.

PURPOSE: Concomitant ophthalmic injuries are common in patients with facial fractures, though frequency varies widely in the literature. Major ophthalmic injuries can have drastic consequences for patients, and permanent visual impairment cannot be prevented in all cases. This study analyzed the frequency and distribution pattern of associated ophthalmic injuries in patients who received operative treatment for fractures of the midface. MATERIAL AND METHODS: The clinical information system was searched for patients with midface fractures that were treated operatively between December 2014 and November 2017. Demographic, fracture-related, and ophthalmic data were assessed and statistically analyzed. RESULTS: This study included 282 patients. The most common fracture types were zygomaticomaxillary complex fractures and orbital floor fractures. Falls and violence were the most common causes of fractures (43.3% and 24.5%, respectively). Chemosis and subconjunctival bleeding were the most common associated eye injuries. The most prevalent long-term eye injury was diplopia, which was identified in 18.4% of cases preoperatively. Postoperative diplopia persisted in 36 cases (12.8%) at 3-month follow-up. Optic neuropathy, enophthalmos, exophthalmos, and retrobulbar hematomas were identified infrequently. CONCLUSION: Minor ophthalmic injuries, including chemosis and subconjunctival bleeding, are more frequently associated with midface trauma. These minor injuries tend to heal quickly and without sequela. Major ophthalmic injuries, including retinal detachment, optic neuropathy, and retrobulbar hematomas, are identified less frequently. Special attention should be paid to patients with diplopia, as this condition may persist and have long-term occupational consequences. Therefore, close interdisciplinary collaboration is essential when treating patients with fractures of the midface to prevent permanent visual impairment.

Does Zygomatic Complex Symmetry Differ Between Healthy Individuals and Surgically Treated Patients Using Intraoperative 3-Dimensional Cone Beam Computed Tomographic Imaging?

PURPOSE: Reconstruction of symmetry after zygomaticomaxillary complex (ZMC) fractures is essential for esthetic appearance as well as function. Therefore, this study aimed to analyze whether bony facial symmetry in patients surgically treated for unilateral ZMC fractures via intraoperative imaging differs from that of healthy individuals. PATIENTS AND METHODS: Retrospective and cross-sectional radiographic measurements of patients treated for unilateral ZMC fractures via intraoperative cone beam computed tomography (CBCT) were performed to evaluate the postoperative ZMC symmetry. The same number of healthy individuals without any history of midfacial trauma matched for age and gender served as the control group. Asymmetry of the ZMC was determined by measuring bilateral differences in the malar eminence position on CBCT. In addition, demographic statistics, etiology, and fracture type were analyzed. RESULTS: Analysis of 57 surgically treated patients and 57 healthy individuals with a mean age of 29 years was performed. No significant difference in the symmetry of the malar eminence position was observed between healthy individuals and patients treated for a unilateral ZMC fracture (P = .890). In one third of patients, corrections were needed after intraoperative CBCT control. CONCLUSIONS: The results of this study indicate that, on average, a ZMC asymmetry of 1.6 mm is observed in healthy individuals. Furthermore, the use of intraoperative CBCT for the treatment of dislocated ZMC fractures helps to achieve precise anatomic, symmetrical repositioning and is suggested to improve the quality of care.

Success rate 1 year after apical surgery: a retrospective analysis.

PURPOSE: The aim of the current study was the retrospective analysis of the outcomes of teeth treated with apical surgery after a 1-year follow-up period. Furthermore, potential factors associated with the success rate were investigated. METHODS: All patients were treated at the Clinic of Cranio-Maxillofacial and Oral Surgery at the University of Zurich between 2010 and 2017. To be eligible for inclusion, all patients were required to have undergone apical surgery with a retrograde root-end filling, and a 1-year follow-up examination at the University of Zurich. Treatment success at the 1-year follow-up time-point was defined as an absence of clinical complaints and radiographically determined healing. Parameters that were analysed included tooth localisation, periapical index of the preoperative lesion, administration of antibiotics, smoker status, histopathology of the apical lesion, radiographically determined sufficiency of root canal treatment pain and clinical signs of inflammation at the initial examination. RESULTS: A total of 81 teeth fulfilled all the inclusion criteria. At the 1-year follow-up, 91.4% of the teeth exhibited successful clinical and radiographic healing. The type of tooth was significantly associated with the success of the surgery (p = 0.006), but radiological severity of periapical inflammation, lesion histopathology, administration of antibiotics, smoker status, the quality of the root canal treatment, and preoperative pain and clinical signs of inflammation were not. CONCLUSION: The results of the present study suggest that apical surgery with retrograde root-end filling is a reliable therapy for the preservation of teeth. Furthermore, there are limited factors that affect the treatment outcome.

Right ventricular mitochondrial respiratory function in a piglet model of chronic pulmonary hypertension.

OBJECTIVE: We aimed to assess the mitochondrial respiratory capacities in the right ventricle in the setting of ventricular remodeling induced by pressure overload. METHODS: Chronic thromboembolic pulmonary hypertension was induced in 8 piglets over a 12-week period (chronic thromboembolic pulmonary hypertension model). Right ventricular remodeling, right ventricular function, and mitochondrial respiratory function were assessed at 3, 6, and 12 weeks after induction of pulmonary hypertension and were compared with sham animals (n = 5). Right ventricular cardiomyocytes and mitochondrial structure were studied in transmission electronic microscopy after 12 weeks. RESULTS: As of 3 weeks, chronic pressure overload induced right ventricular dilatation, right ventricular hypertrophy, and right ventricular dysfunction. Maladaptive remodeling in the chronic thromboembolic pulmonary hypertension model was confirmed by the decrease of right ventricular pulmonary artery coupling and right fractional area change. Mitochondrial functional assays in permeabilized right ventricular myocardial fibers revealed that oxidative phosphorylation capacities (complex I, complex II, and IV of the mitochondrial respiratory chain) were degraded. Furthermore, no change in substrate preference of mitochondria was found in the overloaded right ventricle. There was a good correlation between maximal mitochondrial oxygen consumption rate and right ventricular pulmonary artery coupling (Pearson coefficient r = 0.83). Transmission electronic microscopy analysis showed that the composition of cardiomyocytes was no different between the chronic thromboembolic pulmonary hypertension group and the sham group. However, mitochondrial structure anomalies were significantly increased in the chronic thromboembolic pulmonary hypertension group. CONCLUSIONS: Mitochondrial respiratory function impairment is involved early in the development of right ventricular dysfunction in a piglet model of chronic thromboembolic pulmonary hypertension. Underlying mechanisms remain to be elucidated.

Guided apicoectomy using a CAD/CAM drilling template.

AIM: Modern microsurgical techniques have increased the success rate of apicoectomy relative to that of traditional approaches. This case report introduces a novel workaround for guided apicoectomy using a patient-specific computer-aided design/computer-aided manufacturing (CAD/CAM) three-dimensional (3D)-printed template. MATERIALS AND METHODS: Apicoectomy was performed on the mesial root of tooth 36 using template-guided trephine drilling, followed by retrograde filling with mineral trioxide aggregate (MTA). Initially, a cone beam computed tomography (CBCT) scan and an intraoral surface scan were imported into the planning software. After superimposition, virtual planning was performed to determine the exact localization for root resection. Subsequently, a tooth-supported drilling template was designed and 3D printed. Endodontic microsurgical approaches, including root-end cavity preparation and root-end filling, completed the surgical treatment. RESULT: The apical resection was easily feasible. There were no postoperative complications. Radiological assessment after a 6-month period showed signs of reossification. CONCLUSION: Guided apicoectomy allowed precise root resection, suggesting that this technique may be advantageous in complex anatomical situations.