Extensive Destruction Research Articles

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways.

Wear particle-induced aseptic loosening is the most common complication of total joint arthroplasty (TJA). Excessive osteoclast formation and bone resorptive activation have been considered to be responsible for extensive bone destruction and prosthesis failure. Therefore, identification of anti-osteoclastogenesis agents is a potential therapy strategy for the treatment of aseptic loosening and other osteoclast-related osteolysis diseases. In the present study, we reported, for the first time, that piperlongumine (PL), a key alkaloid compound from Piper longum fruits, could significantly suppress the formation and activation of osteoclasts. Furthermore, PL effectively decreased the mRNA expressions of osteoclastic marker genes such as tartrate-resistant acid phosphatase (TRAP), calcitonin receptor (CTR), and cathepsin K (CTSK). In addition, PL suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced activations of MAPKs (ERK, JNK and p38) and NF-κB, which down-regulated the protein expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Using a titanium (Ti) particle-induced calvarial osteolysis model, we demonstrated that PL could ameliorate Ti particle-induced bone loss in vivo. These data provide strong evidence that PL has the potential to treat osteoclast-related diseases including periprosthetic osteolysis (PPO) and aseptic loosening.

Lithospheric Conductors Shed Light on the Non‐Uniform Destruction of North China Craton

AbstractLow resistivity in the continental lower crust and uppermost mantle has been commonly observed in both Phanerozoic and Precambrian areas. Given different tectonic history, these conductors could be attributed to different conductive mechanisms. The North China Craton (NCC) is one of typical craton that have suffered from extensive destruction, part of which was modified by Phanerozoic tectonic‐thermal events and the others remain stable cratonic lithosphere. We here present a high‐resolution 3‐D electrical resistivity model from the inversion of magnetotelluric data collected in 183 sites of NCC. Beneath the stable craton in the north part of Ordos Block, an E‐W trending conductor extends from lower crust to uppermost mantle, which can be attributed to the concentration of sulfides/graphite emplaced through oceanic subduction during the Paleoproterozoic assembly of Columbia. The conductors beneath the Taihang Mountains and the south part of Ordos Block also reflect ancient sutures. In contrast, the conductor in mantle beneath the south part of North China Plain (SNCP) reflects an on‐going process of craton destruction relating to the subduction of the Pacific Plate in Cenozoic. The MT data, combined with seismic radial anisotropy model suggest the lower crust and uppermost mantle beneath SNCP is anisotropic. And a significant electrical anisotropic layer with the most conductive direction along N70°W and the anisotropy factor of 6.3 is revealed in the 20–70 km depth by 2‐D anisotropic inversion. We attribute the enhanced conductivity along anisotropy direction to the accumulation of melts in sills, resulting from the upwelling of asthenosphere in Cenozoic.

A Current Review of Systemic Lupus Erythematosus Treatment Using Monoclonal Antibodies

Abstract: Lupus is a heterogeneous and inflammatory autoimmune disease that affects the immune system of the body. This disease affects multiple tissues and organs. The most frequent kind of lupus is systemic lupus erythematosus (SLE). SLE is an autoimmune illness in which the immune system targets the body's tissues, resulting in extensive inflammation and tissue destruction in the organs involved. Joints, skin, brain, lungs, kidneys, and blood vessels can all be affected. It appears to be a form of B-cell disease in which autoantibodies attack the cells. Systemic lupus erythematosus autoimmune diseases involve different treatment methods. These abnormalities are due to the presence of autoantibodies, and these contribute to the degeneration of the body’s immune system. In this review, we will focus on various therapies, including SLE treatments, such as B-cell therapy, cytokine therapy, interferon targets, and anticomplementary therapies, all of which have become challenging. We will also discuss post-marketing use and ongoing clinical trials, as well as safety and effective doses.

Development or destruction? Impacts of mining on the environment and rural livelihoods at Connemara Mine, Zimbabwe

ABSTRACT This study interrogates the impacts of mining at Connemara Gold Mine on the environment and rural livelihoods for surrounding communities the mine. While we acknowledge that mining is a very lucrative business and one of the major drivers of the Zimbabwean economy, we argue that most of the benefits of mining tend to be enjoyed elsewhere and not by host communities. We roped in the Treadmill of Production and the Resource Curse theories to demonstrate the interplay between capitalism, the environment and local ordinary people’s livelihoods around Connemara mine. Data were collected through interviews with local community residents, leaders and stakeholder organizations with interests in mining who were selected through purposive and snowballing techniques. We collected data over a period of 13 weeks, interviewing twenty-five respondents in the process and undertaking a series of transect walks across the mined site and its adjacent surroundings. We discovered that mining caused extensive environmental destruction, creating artificial hills and open pits as well as promoting massive soil erosion, contaminating water and land with dangerous chemicals making them unusable for productive purposes. As a result, we conclude that mining at the site did not generate wealth for the local populace but for the mine owners and the state while impoverishing the host communities, destroying their livelihoods in doing so. We conclude by arguing that mining at Connemara is a perfect example of how the Treadmill of Production works and an evident testimony of the Resource Curse.

Effects of the\xa02018 Japan Floods on long-term care insurance costs in Japan: retrospective cohort study

BackgroundClimate change has increased the frequency and severity of torrential rains and floods around the world. Estimating the costs of these disasters is one of the five global research priorities identified by WHO. The 2018 Japan Floods hit western Japan causing extensive destruction and many deaths, especially among vulnerable elderly. Such affected elderly would need long-term care due to the various health problems caused by the disaster. A Long-Term Care Insurance (LTCI) system provides care services in Japan. The aim of this study was to evaluate the effect of the 2018 Japan Floods on LTCI costs and service utilization.MethodsThe participants of this retrospective cohort study were all verified persons utilizing LTCI services in Hiroshima, Okayama and Ehime prefectures. The observation period was from 2 months before to 6 months after the disaster. We used Generalized Estimating Equations (GEEs) to examine the association between disaster status (victims or non-victims) and the monthly total costs of LTCI service (with gamma-distribution/log-link) by residential environment (home or facility). Among home residents, we also examined each service utilization (home-based service, short-stay service and facility service), using the GEEs. After the GEEs, we estimated Average Marginal Effects (AME) over all observation periods by months as the attributable disaster effect.ResultsThe total number of participants was 279,578. There were 3024 flood victims. The disaster was associated with significantly higher total costs. The AME for home residents at 2 months after was $214 (Standard Error (SE): 12, p < 0.001), which was the highest through the observation period. Among facility residents, the AME immediately after the disaster increased by up to $850 (SE: 29, p < 0.001). The service utilization among home residents showed a different trend for each service. The AME of home-based services decreased by up to − 15.2% (SE:1.3, p < 0.001). The AME for short-stay service increased by up to 8.2% (SE: 0.9, p < 0.001) and the AME for facility service increased by up to 7.4% (SE: 0.7, p < 0.001), respectively.ConclusionsThe 2018 Japan Floods caused an increase in LTCI costs and the utilization of short-stay and facility services, and a decrease in utilization of home-based services.

Oxeiptosis: a novel pathway of melanocytes death in response to oxidative stress in vitiligo

Vitiligo is a cutaneous depigmenting autoimmune disease caused by the extensive destruction of epidermal melanocytes. Convincing data has defined a critical role for oxidative stress in the pathogenesis of vitiligo. Oxeiptosis is a caspase-independent cell death modality that was reportedly triggered by oxidative stress and operative in pathogen clearance. However, whether oxeiptosis exists in oxidative stress-induced melanocytes demise in vitiligo remains undetermined. In the present study, we initially found that other cell death modalities might exist in addition to the well-recognized apoptosis and necroptosis in H2O2-treated melanocytes. Furthermore, AIFM1 was found to be dephosphorylated at Ser116 in oxidative stress-induced melanocytes death, which was specific to oxeiptosis. Moreover, KEAP1 and PGAM5, upstream of the AIFM1 in oxeiptosis, were found to operate in melanocytic death. Subsequently, the KEAP1-PGAM5-AIFM1 signaling pathway was proved to be involved in oxidative stress-triggered melanocytes demise through the depletion of KEAP1 and PGAM5. Altogether, our study indicated that oxeiptosis might occur in melanocytes death under oxidative stress and contribute to the pathogenesis of vitiligo.

Value Erosion and the Need for Spiritual Basis of Education

Education is considered as the foundation upon which the entire edifice of the moral culture of an individual is to be constructed. Education should aim at producing this complete man or whole man with a harmonious all round development of personality i. e. physical, mental, social, moral and spiritual. Education in ancient India aimed at producing this whole man. At a later period, the Buddhist and Jain philosophy of education also insisted on morality, non-violence, self-control, austerity, sacrifice and service to the humanity. In spite of merciless and extensive destruction during the medieval age, Hindu educational institutions remained a living reality. At a much later period there developed the 'Namaghar' in Assam and 'Bhagvat Tungi' in Odisha which became the centers of mass education in their respective states. However, the system of education introduced by Macaulay in 1835 aimed at producing a volume of loyal white collar Indian employees for British administration. This led to the complete devastation of Indian values in the education system of India. This paper discusses about the degradation of values in the education system of India and suggests measures to work for the implementation of value education in the schools of India.

Mid-term results of mitral valve reconstruction with autologous pericardial patch for active infective endocarditis with extensive leaflet destruction.

This study aimed to evaluate the outcomes of our repair technique using autologous pericardial patches for active infective endocarditis with extensive mitral valve destruction. From 2009 through 2016, 12 patients with extensive mitral leaflet destruction due to infective endocarditis underwent mitral valve repair with an autologous pericardial patch. Mid-term clinical outcomes and echocardiographic findings of these patients were retrospectively assessed. The perioperative mortality rate was 8.3% (1/12). Postoperatively, the mitral regurgitation grade was ≤ 1 + in all patients. During 5.0 ± 3.2years of follow-up, there was no recurrence of infective endocarditis or death. There were no cases of mitral regurgitation grade > + 1 and pressure gradient > 5mmHg during follow-up among 6 patients who underwent posterior leaflet reconstruction, whereas elevation of the pressure gradient was observed in patients who underwent reconstruction of two areas of the anterior leaflet and survived up till the follow-up phase among 3 patients who underwent anterior leaflet repair. The mitral regurgitation grade worsened and pressure gradient was elevated during the follow-up phase in the 2 patients who underwent bi-leaflet repair, and reoperation was performed. Mitral valve reconstruction using autologous pericardial patch is a useful treatment option for extensive mitral valve destruction due to active infective endocarditis. Our clinical data revealed that good mid-term results were obtained for posterior leaflet lesions, while extensive anterior leafletand bi-leaflet lesion repair did not yield satisfactory results. The indication for surgical repair should be carefully evaluated when an extensive anterior region is involved.

Giant necrotizing cavities in a young individual with septic shock

A 30-year-old Moroccan man presented to our institution with general deterioration and respiratory symptoms evolving over several months. Shortly after admission, he developed progressive respiratory failure, septic shock and cardiomyopathy. A diagnosis of severe Mycobacterium tuberculosis infection was made. Despite appropriate antimicrobial therapy, aggressive respiratory and hemodynamic support, the patient had a fulminant course and died of refractory shock. Chest computed tomography scan showed extensive parenchymal destruction and multiple necrotizing cavities. Here, we review the causes leading to giant necrotizing pulmonary cavities and discuss mycobacterium-related septic shock.

Invasive Broncho-Pulmonary Mucormycosis (IBPM) Misdiagnosed as Tuberculosis

Hemoptysis is nonspecific respiratory symptom with variable etiological factors ranging from infections like tuberculosis, pneumonia, fungal infections to malignant lung process. Although Tuberculosis is leading cause of hemoptysis and reason for empirical treatment and delay in diagnosis, computerized tomography and fiberoptic bronchoscopy has made real change towards approach in management of these cases presented with nonspecific symptoms. In this case report, we have documented ‘invasive bronchopulmonary Mucormycosis’ as cause of recurrent hemoptysis and persistent pulmonary opacity on chest radiograph irrespective of best possible conventional treatment including higher antibiotics and blanket cover of anti-tuberculosis treatment for 4 months. We have documented ‘Reverse halo sign’ on chest CT imaging and final diagnosis established with Bronchoscopy guided lung biopsy showing ‘presence of fungal infection causing extensive parenchymal necrosis, angioinvasion and cartilage destruction along with bronchiolar invasion.’ Caution should be taken during biopsy of these hypervascular lesions as propensity to have post-biopsy ‘catastrophic massive hemoptysis.’ We have also documented near total complete resolution of airway and lung lesions to medical management including Amphotericin and Posaconazole.

MiR-204-containing exosomes ameliorate GVHD-associated dry eye disease.

Graft-versus-host disease (GVHD)–associated dry eye disease is characterized by extensive inflammatory destruction in the ocular surface and causes unbearable pain and visual impairment. Current treatments provide limited benefits. Here, we report that exosomes from mesenchymal stromal cells (MSC-exo) administered as eye drops notably alleviate GVHD-associated dry eye disease by suppressing inflammation and improving epithelial recovery in mice and humans. In a prospective clinical trial, 28 eyes with refractory GVHD–dry eye disease exhibited substantial relief after MSC-exo treatment, showing reduced fluorescein scores, longer tear-film breakup time, increased tear secretion, and lower OSDI scores. Mechanistically, MSC-exo reprogramed proinflammatory M1 macrophages toward the immunosuppressive M2 via miR-204–mediated targeting of the IL-6/IL-6R/Stat3 pathway. Blockade of miR-204 abolished the effects of MSC-exo, while overloading L929-exo with miR-204 markedly attenuated dry eye. Thus, this study suggests that MSC-exo are efficacious in treating GVHD-associated dry eye disease and highlights miR-204 as a potential therapeutic agent.

Casuistry of neck injuries with extensive destruction of the pharynx and larynx

The casuistry of traumatic neck injuries and, in particular, destruction of the upper airway tube cannot exhaust all individual clinical observations. There are still quite a few cases of peculiar forms and nature of injuries and, in terms of their content, sharply different from each other, often complex in their volume, fatal in their consequences and dangerous in complications. Each such individual case needs a detailed description and description in order to analyze this case with greater completeness and clinical coverage.

Linking deep CO2 outgassing to cratonic destruction.

Outgassing of carbon dioxide from the Earth's interior regulates the surface climate through deep time. Here we examine the role of cratonic destruction in mantle CO2 outgassing via collating and presenting new data for Paleozoic kimberlites, Mesozoic basaltic rocks and their mantle xenoliths from the eastern North China Craton (NCC), which underwent extensive destruction in the early Cretaceous. High Ca/Al and low Ti/Eu and δ26Mg are widely observed in lamprophyres and mantle xenoliths, which demonstrates that the cratonic lithospheric mantle (CLM) was pervasively metasomatized by recycled carbonates. Raman analysis of bubble-bearing melt inclusions shows that redox melting of the C-rich CLM produced carbonated silicate melts with high CO2 content. The enormous quantities of CO2 in these magmas, together with substantial CO2 degassing from the carbonated melt–CLM reaction and crustal heating, indicate that destruction of the eastern NCC resulted in rapid and extensive mantle CO2 emission, which partly contributed to the early Cretaceous greenhouse climate episode.

Destroyed Lung Syndrome: A Review of 31 Published Cases

Background: Destroyed lung is a lung condition commonly caused by tuberculosis. Other causes include bronchiectasis, aspergilloma, emphysema, etc. It is characterized by extensive lung destruction and reduced lung function. Chest X-ray, chest CT, bronchography, and ventilation-perfusion ratio scan are the commonest radiologic diagnostic tools. Treatment of choice may include pneumonectomy. The study aims to highlight the common causes of destroyed lung and the major presenting complaints based on age, sex and affected lungs. Method: Published cases from English medical journals were evaluated and analyzed. Results: 31 published cases on destroyed lung were reviewed. 58.1% showed that the left lung was the most commonly affected lung. The condition was more common in males (71%). Based on our review, the commonest causes are pneumonia and tuberculosis at 25.9% and 22.8%, respectively. Conclusion: Pneumonia and Tuberculosis seem to be the commonest causes of destroyed lung based on our review, with left sided affectation being more predominant.

Profile of paediatric tuberculosis mastoiditis -a case series

Tuberculosis (TB) otitis media is an uncommon site of extrapulmonary TB and can primarily present as a complicated TB mastoiditis (TBM). This complication is rare in children, even in TB endemic areas but necessitates early identification as delays can lead to severe morbidities. We describe the clinical characteristics as a case series to raise awareness of the condition, and highlight fundamentals related to diagnosis and management.A retrospective chart review of clinical and radiological information of five children with TBM seen at the Red Cross War Memorial Children's Hospital in Cape Town, South Africa, over the last 5 years. Variables collected included symptomatology, duration of disease, investigations and management.All were under 5 years of age and presented with typical features of acute bacterial mastoiditis. Mean duration of symptoms was 12 days (range 3-30 days). Two children had known TB contacts. Two children had pulmonary involvement, one with miliary TB. CT of the temporal bone demonstrated extensive bony destruction of the petromastoid and demineralised ossicles in all cases. Three children had intracranial extension. Four children demonstrated hearing loss between 30 dB and 83 dB. Necrotising granulomatous inflammation was present in the mastoid specimens in all cases. Confirmatory diagnosis was made via GeneXpert polymerase chain reaction (PCR) (2), Ziehl-Nielson (ZN) stain (1) or a positive TB culture (2). Postoperatively, one patient had normal hearing, two patients had mild conductive hearing loss (CHL), one had mild-moderate CHL and one had profound hearing loss.Delays in identification and management result in marked bony destruction and hearing loss. Radiological and surgical findings typical of TBM, therefore, require tissue sampling from the ear for urgent microscopic, PCR and histologic testing, allowing the avoidance of a mastoidectom. In a TB endemic setting, children with typical findings and necrotising granulomatous inflammation on histology should be considered for prompt commencement of anti-TB therapy while awaiting a definitive diagnosis.

Sociogeografske determinante uništenih srpskih crkava i manastira na Kosovu i Metohiji od 1999. do 2022. godine

Throughout its spiritual, historical, and cultural life in the territory of Kosovo and Metohija, the Serbian Orthodox Church has shared fate with the Serbian people. In the past two decades, from 1999 to 2022, in addition to persecutions of the Serbian Orthodox population in Kosovo and Metohija by the local Albanians, we have also witnessed extensive destruction of Serbian cultural heritage, which is the research subject of this paper. With the application of the social and geographic research methodology, the aim of this paper is to gain scientific insight for the purpose of direct confirmation, substantiated by relevant documents, and presentation of all known cases of aggravated and substantial destruction, desecration, and vandalism of Serbian sacral heritage committed by members of the Albanian community in the territory of Kosovo and Metohija between 1999 and 2022.

Wildfire Susceptibility Mapping Using Five Boosting Machine Learning Algorithms: The Case Study of the Mediterranean Region of Turkey

Forest fires caused by different environmental and human factors are responsible for the extensive destruction of natural and economic resources. Modern machine learning techniques have become popular in developing very accurate and precise susceptibility maps of various natural disasters to help reduce the occurrence of such calamities. The present study has applied and tested multiple algorithms to map the areas susceptible to wildfire in the Mediterranean Region of Turkey. Besides, the performance of XGBoost, CatBoost, Gradient Boost, AdaBoost, and LightGBM methods for wildfire susceptibility mapping is also examined. The results have revealed the higher testing accuracy of CatBoost (95.47%) algorithm, followed by LightGBM (94.70%), XGBoost (88.8%), AdaBoost (86.0%), and GBM (84.48%) algorithms. Resultant wildfire susceptibility maps provide proper inventories for forest engineers, planners, and local governments for future policies regarding disaster management in Turkey.

Prekid arterijske kolateralne mreže kao uzrok amputacije potkolenice nakon konkvazacije uzrokovane motokultivatorom - studija slučaja

Introduction. Leg conquassation caused by petrol tiller is one of the most severe injuries in bone and joint traumatology. Firm strokes by sharp tiller blades produce strong force that easily damages both soft tissues and bones. Since tillers are used in soil processing, the wounds are highly contaminated with dirt and fertilizers, hence the anaerobic spore-forming bacilli, such as tetanus and gas gangrene pathogens. Case report. This paper presents the treatment of a 69 years old man with chronic arterial insufficiency of the lower extremities who suffered severe injury of the lower leg (IIIB open tibial fracture according to Gustillo) by petrol tiller while performing agricultural work. Due to the absence of pulsations, Multislice CT angiography and arteriography were performed. Arteriography of the injured leg confirmed chronic occlusion of the anterior tibial artery and numerous stenotic lesions of the peroneal and posterior tibial arteries. Posterior tibial artery was chronically occluded in its distal part and connected to the foot with moderately developed collateral arteries which provided the viability of the injured leg. Despite undertaken basic principles of treatment of this serious injury (primary surgical treatment of wounds, external fixation, reconstruction of soft tissue, antibiotic and anti-tetanus prophylaxis) due to infection and gangrene the treatment ended with lower leg amputation. Conclusion. Leg amputation can be expected in this type of injuries in cases of extensive destruction of tissue in the field of existing chronic arterial insufficiency in elderly patients, even in the absence of injury of main blood vessels due to traumatic disconnection of collateral in such patients.

Postoperative lumbar spondylodiscitis

Background. Several causes that can trigger POD can be incriminated: the patient's immune status, surgical technical errors, intra-operative contamination, foreign materials microfilm. Extensive analysis is required to eradicate the limited or diffuse infection and manage the optimal therapeutic attitude conservative or by surgery to get: faster recovery time, to improve symptoms, to allow mobilization, to offer a good quality of life and to reduce the average length of hospital stay.&#x0D; Objectives. To perform a systematic review of POD outcomes via retrospective analysis of current studies based on the mechanism, the pathogenesis, the management of patient's immunological status, aetiology (microorganism involved, foreign material applied for hemostasis, application of spinal instrumentation, cement, screws, spinal devices), laboratory (TLC, ESR, CRP), MRI/CT-scan, antibiotherapy guidelines and the type of surgery performed: classical or minim-invasive, length of procedure, intraoperative accidents, the experience of the neurosurgeon, post-operative stay in ICU, etc.&#x0D; Methods. Several data were taken into account regarding lumbar infections using a comprehensive review of the literature published studies from 1998 to 2021. Demographic data, clinical variables, length of hospital stay, duration of antibiotic treatment, and post-treatment complications were assessed.&#x0D; Results. We performed a systematic review concerning 31 studies regarding clinical status, diagnosis and treatment.&#x0D; Conclusions. Based on our systematic analysis, training and continuous education in spine surgery are necessary to prevent POD. The diagnosis of lumbar POD is based on history and physical examination, biochemical markers, neuroradiologic studies, using appropriate MRI imaging. Most cases of lumbar POD can be managed by conservative treatment with antibiotics after causative germ isolation and antibiogram. Surgery is performed on patients with conservative treatment failure - resistant to antibiotic therapy, as those with neurological complications: acute paraplegia, pain resistance to analgetics, acute sepsis, abscesses, spinal instability, severe kyphosis. Early surgery with wound irrigation/debridement is more readily able to disrupt biofilm formation and facilitate penetration of systemic antimicrobials to allow for resolution of the infection, vacuum-assisted closure facilitates wound healing and eradicates spinal infections, decrease the rate of complications, permit rapid pain relief while preserving the instrumentation/stability, better clinical outcomes, infection control before extensive destruction of the vertebrae, spinal instability and kyphotic deformity appear. Instrumentation can usually be preserved in patients with early infections (e.g., &lt;6 weeks), but instrumentation removal should be considered for infections presenting in a delayed fashion (e.g., &gt;6 weeks to even years) PSII. Patients should be adequately followed for one postoperative year, to ensure that the infection has been fully eradicated. Implant sonication provides cultures for direct identification of active and/or persistent biofilm, while the introduction of enzymes that dissolve the biofilm matrix (e.g., DNase and alginate lyase) and quorum-sensing inhibitors that increase biofilm susceptibility to antibiotics may further help manage postoperative infection (2)(27-31).

Rehabilitation of severely-destructed endodontically treated premolar teeth with novel endocrown system: Biomechanical behavior assessment through 3D finite element and in vitro analyses

ObjectiveRehabilitation of endodontically treated premolars with extensive coronal destruction through endocrown approach remains a controversial topic in reconstructive dentistry. There is no clear consensus in the literature which endocrown design with which material is the most effective restoration option for severely-destructed endodontically treated premolars. The aim of this study was to assess the biomechanical behavior of endodontically treated maxillary first premolars restored with a novel endocrown system compared to the conventional one varying the applied load type through finite element and in vitro analyses. Materials and methodsFor finite element analysis, two models representing two endocrown systems used for restoration of severely-destructed endodontically treated maxillary first premolar tooth were generated: Model C for the conventional monolithic IPS e.max CAD endocrown and Model P for the novel bi-layered endocrown (PEKKTON ivory coping veneered with cemented IPS e.max CAD). Modified von Mises stress values on the remaining tooth structure, cement lines and restorative materials were evaluated separately under axial and oblique loading of 450 N. For in vitro analysis, forty sound human bifurcated maxillary first premolars were collected, endodontically-treated, and divided into 2 main groups (n = 20) according to the system used for endocrown fabrication; Group C: the conventional monolithic endocrowns and Group P: the novel bi-layered endocrowns. All specimens were subjected to an artificial thermomechanical aging protocol. Each main group was subdivided into two subgroups (n = 10) according to the loading type (axial and oblique) applied during the fracture resistance test. Qualitative analysis using Stereomicroscopy and Scanning Electron Microscopy was performed. Data were statistically analyzed at p-value ≤ 0.05. ResultsRegarding stress distribution pattern of remaining tooth structure (enamel and dentin), both endocrown systems and cement lines under both axial and oblique load application, Model P resulted in lower stresses than Model C. The oblique stress values of all analyzed structures were higher than corresponding values resulted axially. Considering failure load, a significantly higher load was recorded for Group P when axial or oblique loading was applied (p = 0.00). A significantly higher failure load was recorded with axial loading for both main groups. With regard to failure mode, a statistically significant difference was observed between main groups (p = 0.033), with more favorable failures detected for Group P axially. ConclusionsCompared to the conventional endocrown system, the studied novel system improved the biomechanical behavior within tooth/restoration complex of the restored severely-destructed endodontically treated maxillary first premolar teeth, whatever the applied load type. Clinical significanceThe novel endocrown system using a PEKK coping veneered with cemented IPS e.max CAD can be considered a favorable promising option for restoration of severely-destructed endodontically treated premolar teeth, with more protection for residual tooth structure. It can be considered as a conservative alternative option to the conventional treatment modalities not only for normal clinical conditions, but also for parafunctional cases.