The Neretva dwarf goby Orsinigobius croaticus (Gobiiformes, Gobionellidae) is an endemic fish native to the freshwaters of the Adriatic Basin in Croatia and Bosnia and Herzegovina. Due to its limited distribution range, specific karst habitat and endangered status, laboratory studies on reproductive biology are scarce. We investigated the sound production and acoustic behaviour of this species during reproductive intersexual laboratory encounters. We performed dissection and micro-computed tomography (μCT) scanning of the pectoral girdle to explore the anatomy of its putative sound producing mechanism. To study interspecific acoustic differences and determine whether acoustic features can discriminate among species, comparative analysis was conducted on sounds produced by closely related soniferous sand gobies. Our results indicate that males of the O. croaticus emit pulsatile sounds composed of a variable number of short (~ 15 ms) consecutive pulses when interacting with females, usually during the pre-spawning phase in the nest, but also during courtship outside the nest. Pulsatile sounds were low-frequency and short pulse trains (~ 140 Hz, < 1000 ms), and spectro-temporal parameters were correlated with physical traits and water temperature. Male visual behaviour rate was higher when co-occurring with sounds and females entered the male’s nest significantly more frequently when sounds were present. Male sound production was accompanied by movements such as head thrust and fin spreading. μCT scans and dissections suggest that O. croaticus shares certain anatomical similarities of the pectoral girdle (osseous elements and arrangement of levator pectoralis muscles) to previously studied sand gobies. Multivariate comparisons, using sounds produced by eight soniferous European sand gobies, effectively distinguished soniferous (and sympatric) species based on acoustic properties. Discrimination success decreased when temperature-dependent features (sound duration and pulse repetition rate) were excluded from analysis. Therefore, we suggest both spectral and temporal features are important for acoustic differentiation of sand gobies.

The plants’ geographical distribution is affected by natural or human-induced climate change. Numerous studies at both the global and regional level currently focus on the potential changes in plant distribution areas. Ecological niche modeling can help predict the likely distribution of species according to environmental variables under different climate scenarios. In this study, we predicted the potential geographic distributions of Quercus ilex L. (holm oak), a keystone species of the Mediterranean ecosystem, for the Last Interglacial period (LIG: ~120 Ka), the Last Glacial Maximum (LGM: ~22 Ka), mid-Holocene (MH: ~6 Ka), and future climate scenarios (Representative Concentration Pathway (RCP) 4.5 and 8.5 scenarios) for years 2050-2070 obtained from CCSM4 and MIROC-ESM global climate scenarios respectively. The models were produced with algorithms from the R-package “biomod2” and assessed by AUC of the Receiver Operating Characteristic plot and True Skill Statistics. Apart from BIOCLIM (SRE), all model algorithms performed similarly and produced projections that are supported by good evaluation scores, although Random Forest (RF) slightly outperformed all the others. Additionally, distribution maps generated for the past period were validated through a comparison with pollen data acquired from the Neotoma Pollen Database. The results revealed that southern areas of the Mediterranean Basin, particularly coastal regions, served as long-term refugia for Q. ilex, which was supported by fossil pollen data. Furthermore, the models suggest long term refugia role for Anatolia and we argue that Anatolia may have served as a founding population for the species. Future climate scenarios indicated that Q. ilex distribution varied by region, with some areas experiencing range contractions and others range expands. This study provides significant insights into the vulnerability of the Q. ilex to future climate change in the Mediterranean ecosystem and highlights the crucial role of Anatolia in the species’ historical distribution.

with other laboratory and clinical investigations. Early and accurate diagnosis of inherited conditions generally leads to better medical care for patients and their families, with improved knowledge of the natural history of the condition and early intervention. It is therefore essential that equitable access to such testing is established for indigenous and isolated populations, in order to further narrow the health disparity gap. Although supported by funding from a few sources, this study signals a success for the Silent Genomes Project, with one of the cases having been identified by whole genome sequencing within that project, after negative whole exome sequencing. Furthermore the study has potential life-changing clinical consequences and provides starting points for possible interventions for respiratory medicine in the Inuit population. These include increased awareness of the possibility of PCD in patients presenting with neonatal respiratory distress, bronchiectasis or otitis media leading to early intervention; and in conjunction with Inuit organizations and public health officials, targeted analysis of the DNAH11 variant in the population with the possible introduction of newborn screening for PCD.

Introduction: Wearable Cardioverter Defibrillator (WCD) is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD). Many of these patients also present with atrial fibrillation (AF). However, the rate of WCD-detected ventricular or atrial arrhythmia events in this specific high-risk cohort is not well understood. Methods: In WEARIT-II, the cumulative probability of any sustained or non-sustained VT/VF (WCD-treated and non-treated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan-Meier method by prior AF, with comparisons by the log-rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient-years, and were analyzed by prior AF using negative binomial regression. Results: WEARIT-II enrolled 2000 patients, 557 (28%) of whom had AF prior to enrollment. Cumulative probability of any sustained or non-sustained WCD-detected VT/VF during WCD use was significantly higher among patients with a history of AF than without AF (6% vs. 3%, p=0.001). Similarly, the recurrent rate of any sustained or non-sustained VT/VF was significantly higher in patients with prior AF vs. no prior AF (131.5 events per 100 patient-years vs. 22.7 events per 100 patient-years, p=0.001). Patients with prior AF also had a significantly higher burden of any WCD-detected atrial arrhythmias/SVT/inappropriate therapy (183.2 events per 100 patient-years vs. 74.8 events per 100 patient-years, p<0.001). Conclusion: Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation.

People with mpox are likely to be stigmatized because of analogies to other sexually transmitted infections. Stigma is driven by beliefs about the perceived severity of the condition and perceived responsibility for acquiring the condition, both in broader society and individual responsibility. We explored these beliefs and compared them across mpox, HIV, syphilis, gonorrhoea, and chlamydia in an online survey, conducted in July, 2022, with 394 men-who-have-sex-with-men (MSM) in the Netherlands. We compared mean scores between infections using repeated measures ANOVA and conducted hierarchical regression analyses to identify determinants of both mpox perceived responsibility endpoints. Results showed that participants expected that mpox would be seen as a ‘gay disease’ and will be used to blame gay men. Compared to other infections, mpox was considered less severe than HIV, but more severe than syphilis, gonorrhoea, and chlamydia. Perceived responsibility was comparable across infections, but, for each infection, participants perceived attributed responsibility for infection to be higher in society than individual responsibility. Both perceived responsibility endpoints were highly correlated with each other and with other stigma beliefs. These results provide insight on the underlying determinants of mpox stigma, and demonstrate that mpox stigma is present in the Netherlands.

Summary: This paper proposes a 1/f noise optimized correlated multiple sampling (NOCMS) technique based on differentiated sampling weights for CMOS image sensor. Transfer functions of standard CMS and NOCMS for analyzing the suppression effect of random noise respectively are derived based on the Fourier Transform theory. NOCMS shows a dramatic advantage in the suppression of 1/f noise. For implementing NOCMS, the ramp generator provides multiple sets of ramps with different slopes to quantize the reset and signal voltages. Sampling weights are increased with the decrease of ramp slopes. The last reset and first signal values are weighted more due to their potentially higher correlations. Simulation results under 110nm CMOS technology illustrate that the ADC achieves DNL of −0.80/+0.70LSB and INL of −0.70/+0.90LSB after the NOCMS operation. The input-referred random noise is 142.9µV rms under standard CMS and 120.9µV rms under NOCMS when the number of samples equals 8. The noise reduction effect is improved by 15%. NOCMS makes it possible to further reduce 1/f noise of CMOS image sensor.

Cardiovascular diseases (CVDs) are complex, encompassing many types of heart pathophysiologies and associated etiologies. It has been shown that fractionated radiation exposure at high doses (3-17 Gy) to the heart increases the incidence of CVD, as evident from radiotherapy studies. However, the effects of low doses of radiation on the cardiovascular system or the effects from space travel, where radiation and microgravity are important contributors to damage, are not clearly understood. Herein, the adverse outcome pathway (AOP) framework was applied to develop an AOP to vascular remodeling from the deposition of energy. Following the creation of a preliminary pathway with the guidance of field experts and authoritative reviews, a scoping review was conducted which informed final key event (KE) selection and facilitated evaluation Bradford Hill criteria of the key event relationships (KERs). The AOP begins with a molecular initiating event of deposition of energy; ionization events increase oxidative stress, which concurrently causes the release of pro-inflammatory mediators and alters signaling pathways. These KEs alter nitric oxide levels leading to endothelial dysfunction and subsequent vascular remodeling (the adverse outcome). The work identifies evidence needed to strengthen understanding of the causal associations for the KERs, emphasizing where there are knowledge gaps and uncertainties in both qualitative and quantitative understanding. The AOP is anticipated to direct future research to better understand the effects of space on the human body and potentially develop countermeasures to better protect future space travelers.

{The use of state estimation techniques offers a means of inferring rotor effective wind speed from standard measurements of wind turbines. Typical wind speed estimators rely upon a pre-computed quasi-steady aerodynamic mapping, which describes the relationship between pitch angle and tip-speed ratio and the power coefficient. In practice, the static mapping does not capture the influence of turbine structural dynamics and atmospheric turbulence, inevitably resulting in poor performance of the wind speed estimation. In addition, the turbine aerodynamic properties might not be easily accessible. Thus, this paper presents a rotor effective wind speed estimation method that obviates the requirement for prior knowledge of turbine power coefficients. Specifically, the proposed method exploits a simple actuator disc model, where the aerodynamic power and thrust coefficients can be characterised in terms of axial induction factors. Based on this insight and standard turbine measurements, real-time estimation of rotor effective wind speed and axial induction factors can then be achieved using a simplified turbine drive-train model and an extended Kalman filter. In addition, the actuator disc model can be updated easily over time by calibrating solely two correction factors. Thus, the proposed algorithm presents an alternative for estimating the rotor effective wind speed, which is valuable for numerous applications, for example, LiDAR-assisted control and coherence studies.

Delayed cerebellar ataxia induced by Plasmodium falciparum malaria: A rare complicationEmmanuel Edwar Siddig1,2,*, Sarah Misbah EL-Sadig3, Hala Fathi Eltigani1, Ahmed Mudawi Musa4, Nouh Saad Mohamed5, Ayman Ahmed4,6,71 Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan2 Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan.3 Faculty of Medicine, University of Khartoum, Khartoum, Sudan4 Institute of Endemic Disease, University of Khartoum, Khartoum, Sudan5 Molecular Biology Unit, Sirius Training and Research Centre, Khartoum, Sudan6 Swiss Tropical and Public Health Institute (Swiss TPH), Allschwil 4123, Switzerland7 University of Basel, Petersplatz 1, Basel 4001, Switzerland* Correspondance: Emmanuel Edwar Siddig; University of Khartoum, Khartoum, Sudan.Email: [email protected]: 0000-0001-6314-7374

A document by Shyam Duvuru. Click on the document to view its contents.

Background: Sickle cell disease (SCD) is characterized by vaso-occlusive crises (VOCs), that impair the health-related quality of life (HRQoL). The aim of this study is to evaluate the impact of hospitalization for VOCs on HRQoL in children with SCD over time. Methods: In this longitudinal cohort study, children aged 8-18 years diagnosed with SCD at the Amsterdam UMC were included between 2012 and 2021. HRQoL was annually measured as part of standard care using the Pediatric Quality of Life Inventory. The impact of hospitalization for VOC on HRQoL was evaluated using linear mixed models 3, 6, 9 and 12 months after hospitalization. The effect of frequency of hospitalization for VOC on HRQoL was evaluated over the last 12 months. Results: In total , 94 children with SCD were included with a median age of 11.8 years (IQR 9-14). Thirty-seven patients (39%) had been hospitalized for a VOC. Hospitalization for VOC led to a decrease of 3.2-4.8 points in total HRQoL compared to patients without hospitalization, most pronounced 3 months after hospitalization. Recurrent admission for VOC in the last 12 months was associated with a decrease of 2.3 points in total HRQoL (p=0.04). The most affected subscale was physical functioning. Conclusion: The adverse effects of hospitalization for VOC in children with SCD persist up to 12 months after hospitalization. After hospitalization for VOC, extra attention and support for its negative impact on HRQoL are recommended. This study also underlines the importance of systematically measuring HRQoL allowing clinicians to intervene accordingly.

Mobile edge computing (MEC) seems to be highly efficient to process the generated data from IoT devices by providing computational resources locating in close range to network edge. MEC can be promising in reduction of latency and consumption of energy from data transmissions from offloading computational tasks from IoT devices to nearby edge servers. In this paper, a computation offloading optimization algorithm is proposed which is based on deep deterministic policy gradient for realistic Aurelia X6 Pro unmanned aerial vehicle (UAV)-assisted MEC systems. The proposed algorithm optimizes the offloading decision for UAVs by taking task characteristics and the communication environment into consideration. The simulation yields outcomes indicating that the suggested algorithm can considerably enhance the competency of MEC systems.

The spatiotemporal variability of groundwater level (GWL) is an important property of peatland hydrology that directly affects fluctuations of water storage. Nonetheless, current understanding of the variations of GWL in different time scales still remains unclear. In this study, two peatland watersheds (0.151 km 2 for W1 and 0.844 km 2 for W2) in the Zoige Basin in the Source Region of the Yellow River (SRYR) were selected for monitoring the temporal variability of GWL using self-recorded water loggers during 2017-2021. The main results demonstrate that: (1) GWL variations tended to be controlled by gully drainage in sites adjacent to the gully and be more synchronized with rainfall in sites distant from the gully. The GWL near the gully that cuts through the peat layer was lower than that near the gully without cutting through the peat layer, with a maximum difference between the former and the latter of 58.3 cm, indicating the effect of longitudinal attenuation of the GWL in W1. (2) Because rainfall had a lag effect on the GWL, the length of lag gradually decreased with increased rainfall intensity (i.e., the lag time of sites far away from the gully was about 18 min shorter than that of sites close to the gully in W1). (3) The peak values of the GWL occurred simultaneously with the maximum and minimum rainfall in W2, and the peak occurrence time was related to the ratio of precipitation to evaporation. In the downstream sites, GWL fluctuated more intensively than the upstream ones in W2. Moreover, the average GWL of the upstream sites was 14.3 cm higher than that of the middle ones, indicating a decreasing trend of water storage along the gully. (4) The GWL discrepancy between wet and dry seasons was explicit, but the difference was smaller in the upstream sites due to limited gully incision and higher water storage within the peat layer. Additionally, rainy days dominate the GWL change in wet and dry seasons, but the different rainfall intensity resulted in a stable GWL in the dry season and an oscillating GWL in the wet season in W2. This study uncovers the spatio-temporal variation of groundwater level in two peatland watersheds, which is of great significance for understanding runoff variation, ecohydrological processes, and wetland shrinkage in the SRYR.

Aspirin induced urticaria in a recently diagnosed ischemic stroke patient: A case report and literature review. Abhinav Dahal : Sukraraj Tropical and Infectious Disease Hospital, Teku, Kathmandu, Nepal Email: [email protected] gautam: Nepalgunj medical college, banke,Nepalemail: [email protected] Shakya : Manipal college of medical sciences, Pokhara, Nepalemail: [email protected] pant: Manipal college of medical sciences, Pokhara, Nepalemail: [email protected] Bhandari , Nepal Medical College, Jorpati, Kathmandu, Nepal [email protected] Babu Shrestha, M Abdur Rahim Medical College, Dinajpur, Bangladesh. [email protected] author:ABS; M Abdur Rahim Medical College, Dinajpur, Bangladesh. [email protected]: Aspirin and urticaria correlation has not been fully understood. The pharmacological inference is suspected to be the diversion of arachidonic acid metabolism. Aspirin sensitivity can aggravate pre-existing chronic urticaria and in some instances causes acute urticaria. We report a case of a 53-year old male, recently diagnosed with stroke, who presented with complaints of multiple rash over trunk and upper extremity with aspirin. NSAIDs induced urticarial are usually neglected by physicians during diagnosis. Keywords: Aspirin, urticarial, stroke, hemiplegiaIntroduction: Aspirin is a drug which is widely used to reduce the risk of stroke, transient ischemic attack, and cardiovascular events. This is due to its antithrombotic properties by irreversibly inhibiting the cyclooxygenase enzyme, reducing the synthesis of Thromboxane A2 and thus subsequently reducing platelet aggregation [1– 3]. Aspirin and NSAIDs’ pharmacological properties also result in adverse reactions like GI upset, renal toxicity, and hemorrhagic complications, as well as potentiate hypersensitivity reactions [4]. Aspirin Hypersensitivity is reported by 0.9 to 1.5% of the general population [5]. Hypersensitivity reactions to NSAIDs are classified on the basis of their involvement of the skin, like urticaria or angioedema, the airways or other organs, their acute or delayed onset, the presence of underlying diseases, and their cross reactivity[6]. In this report, we document a case of aspirin induced urticaria in a patient with a recent history of Ischaemic stroke and Hypertension.Case Description: A 53 years old male presented to the emergency department with a chief complaint of multiple rashes with burning and itching sensation over trunk and extremities. Figure 1 and 2. The patient was a known case of hypertension with recent diagnosis of left sided ischemic stroke with right sided hemiparesis 7 days back for which he was admitted for 3 days. There were no significant reactions to the treatment noticed during the hospital stay. He was discharged with a daily dose of aspirin 75 mg o.d., enalapril 10 mg o.d., atorvastatin 20 mg o.d., omeprazole 20 mg b.d. He was advised for proper bed rest with two hourly posture changes & physiotherapy. He was solely on prescribed medications for the past 4 days. On the next day, he was admitted following the appearance of cutaneous manifestations with no other associated symptoms such as angioedema or shortness of breath. He had no prior history of allergic reactions. On further enquiry, he denied any changes to diet or environmental stimuli including no exposure to any pets or animals. He also gave a negative history of family members having such allergic manifestations. On examination, multiple, pruritic, erythematous, blanching macules were present on bilateral upper extremities and trunk(Figure 1). His vital signs were within normal limits. Leukocytosis (wbc:12,000 cells/mm3) with higher eosinophil count ( 550 per ml of blood) was noted while other complete blood count and comprehensive metabolic panels were unremarkable. Medical history revealed he was taking enalapril 10 mg o.d. for the past 3 years for hypertension. As ACE inhibitors are commonly responsible for causing the side effects such as allergies, drug rash & even angioedema, it was replaced with amlodipine 5 mg o.d. He was started on histacin 4 mg b.d for symptomatic management. However, there was no significant improvement in his condition. Therefore, we decided to stop the current medication one at a time to identify the culprit drug. Aspirin was replaced with clopidogrel 75 mg o.d. & given daily. He was kept under observation & followed up the next day with improvement. Patient told that his itching and the degree of rash spread throught his body were diminished. Three days later, the rashes almost fully subsided & he was advised to continue histacin for 1 more week without stopping clopidogrel intake. Aspirin was identified as the sole cause for the rashes. He was discharged following complete recovery of cutaneous symptoms after 3 days with proper counselling regarding his condition and precaution to be taken for future aspirin use.Discussion: Aspirin and other NSAID are known to cause hypersensitivity reactions. One of the manifestation of such reactions is urticaria. The prevalence of aspirin induced urticaria is estimated to be around 0.3% excluding individuals with recurrent urticaria, hay fever and chronic chest disease [7]. Aspirin induced Urticaria(AIU) can be classified into two types as aspirin intolerant acute urticaria(AIAU) and aspirin intolerant chronic urticaria(AICU). The symptoms develop within minutes to 24 hour in AIAU and lasts for less than 6 weeks whereas, in AICU symptoms typically last for more than 6 weeks.[8] Elevated IgE levels and atopy are suggested as a common predisposingfactors for AIU according to a genetic study done in Korean population[8]. In addition, HLA-DRB1 * 1302 - DQB1*0609 also has been identified as a genetic marker[9]. Besides this, various genetic studies have reported that high affinity IgE receptor[10] , histamine N‐methyltransferase[11] and adenosine A3 receptor[12] are other genetic determinants for AIU. These findings allude that, causes leading to the release of inflammatory mediators either by increased histamine release, faulty histamine degradation or augmented mast cell signalling, contributes to the manifestation of AIU. NSAIDs and Aspirin are known to be one of the common drugs causing hypersensitivity drug reactions.(13) Drug Hypersensitivity Reactions constitute about one third of all adverse drug reactions and affects 10-20% of hospitalized patients and 7% of outpatients.[14] Depending on the type of hypersensitivity reaction, patient can develop an array of cutaneous manifestations ranging from urticaria/ angioedema, fixed drug eruption, maculopapular exanthem to more severe manifestations such as DRESS or SJS/TEN.[15] We have previously encountered a case of Stevens Johnson Syndrome, Type III Hypersensitivity Reaction due to an antibiotic namely Cefixime.[16] In this case, we have encountered a case of Single NSAID Induced Urticaria/ Angioedema or Anaphylaxis, a Type I Hypersensitivity Reaction. Figure 3.To date, there are only few case reports published in pubmed highlighting the association of aspirin with urticaria. This may be due to the fact that aspirin sensitivity is often neglected because of the cross reaction with NSAIDs. One case report has documented urticaria in three patients caused by aspirin where pharmaceutical excipients present in the formulation of drug was found to be the sole cause for the hypersensitivity reaction in two of those patients.[17]However, acute urticaria is not uncommon and when patients present with an urticarial reaction clinicians do not consider NSAIDs as the cause, as the reaction occurs in context of different triggers and is thus difficult to establish.Beyond drug induced urticaria, differential diagnosis of acute urticaria includes urticaria attributed to infections, foodstuffs, contact dermatitis, solar urticaria, cholinergic urticaria, arthropod bite reactions, autoimmune disorders, small vessel vasculitis. Diagnostic workup for many of these etiologies rely on laboratory parameters and histological evidence in addition to history. Initial laboratory investigations revealed lekocytosis with a predominance of eosinophils. However, access to further testing was limited due to patient’s refusal and unfortunately no blood investigations or skin biopsy was taken at presentation. Management of NSAID induced urticaria includes strict culprit NSAID avoidance along with symptomatic management of acute urticaria.[18] Antihistamines are the first line treatment for management of acute urticaria. In severe cases, corticosteroids can be added to control symptoms.[19,20] Some types of NSAID hypersensitivity are known to exhibit cross reactivity thus strict NSAID avoidance should be done until potential of cross-intolerance is ruled out. If patient has history suggesting selective NSAID induced urticaria, challenge to chemically unrelated strong COX-1 inhibitor may be done to rule out crossreactivity type hypersensitivity.[21] Once diagnosis of SNIUAA is established, use of drug allergy passport and patient education help both the medical provider and the patient know about the NSAID hypersensitivity status, avoidance of the culprit NSAID as well as use of chemically unrelated NSAIDs as safe alternatives. In this entity, alternative drug to aspirin must be sought.[18,21] Therefore our clinical reasoning is composed from detailed patient’s history, physical examination and clinical course. Our patient did not have any history of multisystem involvement, recent infection, past medical history of atopy, inducible urticaria due to heat, cold or stress, recent contact with common irritants or insect bite. The patient had been taking Aspirin, Enalapril and Atorvastatin following the diagnosis of Ischemic Stroke with Right Sided Hemiparesis. The urticaria and pruritus should not be caused by Enalapril, since the patient was tolerating the medication well for the past 3 years and the patient’s symptoms worsened even after withdrawing of the drug. The temporal correlation between the appearance of urticarial rash and aspirin intake, and the resolution of urticarial rash and pruritus following aspirin discontinuation suggests the possibility of Aspirin Induced Urticaria. The causality assessment of the adverse drug reaction (ADR) was carried out using the Naranjo Scale, a method for estimating the probability of adverse drug reactions. The assessment revealed the ADR to be ‘Probable’(+6) to be associated with Aspirin.[22]The patient’s history notably lacked presence of chronic urticaria. While the drug provocation test for cross intolerance was not done, the patient’s history reveals previous tolerance to other NSAIDs like ibuprofen and paracetamol.

Functional and Aesthetical Full Mouth Rehabilitation of a patient with severely worn Dentition and Deep bite: A 3-Year Follow-UpNegin Yaghoobi1, Azam Mostafavi2 , *Soolmaz Barati 31 Assistant Professor, Dental Research Center, Dentistry Research Institute, Department of Prosthodontics, Tehran University of Medical Science, Tehran,2 Associate Professor, Dental Research Center, Dentistry Research Institute, Department of Prosthodontics, Tehran University of Medical Science, Tehran,*3 Postgraduate Prosthodontics Resident, Dental Research Center, Dentistry Research Institute, Department of Prosthodontics, Tehran University of Medical Science, Tehran, Iran.CorrespondenceSoolmaz Barati , Department of Prosthodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran 1439955991, Iran.Email: [email protected] Clinical Message:Full mouth reconstruction in a patient with deep bite and bruxism and worn dentition is a challenging situation. Minimally invasive approach by using CAD-CAM restorations is recommended in these cases.AbstractFull mouth reconstruction of a deep bite patient with severely worn dentition is a challenging situation for the prosthodontists. This study represents minimally invasive procedures in mentioned condition without increasing vertical dimension. After 3 years of follow up no complication was observed.Keywords: Bruxism, Full mouth reconstruction, Tooth wear, Computer-Aided DesignINTRODUCTIONTooth surface loss (TSL) or tooth wear (TW) is an irreversible loss of hard teeth structure which is observed clinically as attrition, abrasion, abfraction and erosion (1). Different types of tooth wear frequently coexist, making it difficult to determine the type of wear present (2).Abrasion is defined as physical wear of the teeth caused by something other than tooth-to-tooth contact like inappropriate toothbrushing or repeated use of a toothpick (2). Furthermore, the loss of tooth structure may occur when the teeth are in contact with one another, as a result of attrition or dental erosion caused by acids in the mouth. An abfraction, a wedge-shaped lesion with sharp line angles, has been attributed to eccentric forces acting on the natural dentition (3), whereas Dawson believed it is the result of tooth brushing rather than occlusal overload (4, 5).Severe tooth wear could cause tooth hypersensitivity related to dentine exposure, morphological change of occlusal surfaces of teeth, occlusal disharmony, functional impairment, temporomandibular joint disorders (TMD) and also poor aesthetic (1, 6, 7). In addition, loss of occlusal vertical dimension (OVD) may lead to dentoalveolar compensation or increased interocclusal rest space (8).Due to progress in restorative methods and modified materials there are many treatment options for patients with worn dentition such as: conventional full coverage restorations, direct or indirect composite resin restorations, cast adhesive alloys (metal palatal veneers) and bonded ceramic restorations (9).Malocclusion, which can be defined as ”an abnormal occlusion in which teeth are out of alignment with adjacent teeth in the same jaw or the opposing teeth when the jaws are closed” (3), can result in oral health complications if left untreated. As a specific type of malocclusion, deep bite is defined as an increased vertical overlap between the upper and lower incisors which is treated by several methods range from removable appliances to fixed appliances with or without orthognathic surgery (10); It is however believed that deep overbite with stable holding contacts constitute one of the most stable dentitions, in which case no dental treatment is necessary (5).Although restoration of worn teeth by reorganizing the occlusion at an increased VDO has been well documented, some complaints, such as TMD, chipping of unsupported ceramics, and relapse to previous conditions are frequent (6, 7, 11). For worn teeth with insufficient restorative space, intentional endodontic treatment, crown lengthening, and full coverage restorations have been recommended (5, 12).While full coverage restorations have been recommended to restore worn teeth with insufficient restorative space, based on the available literature, conservative approaches such as minimally invasive restorations have been found to be more conservative than conventional procedures (13, 14).A few examples of minimally invasive approaches that might be indicated in such worn dentition include establishing occlusal harmony with an ideal occlusal plane through laminate veneer restorations, as well as occlusal veneers (15-17).Consequently, a full-mouth rehabilitation involving an interdisciplinary approach for a patient with severe deep bite and worn dentition is described in this clinical report.CASE PRESENTATIONA 54- year-old man was referred to the department of prosthodontics for oral rehabilitation. His chief complaint was being worry about worn dentition and poor esthetic especially in anterior teeth. There was no specific diet or mal habit mentioned by the patient other than clenching and bruxism during the night. Extra oral examination revealed almost symmetrical esthetic proportions and no limitations or deviation was observed during maximum mouth opening. palpation of muscles, lymph nodes, and temporomandibular joints confirmed normal conditions. Intraoral examination revealed uneven incisal plane, smile disharmony and uneven gingival plane in both arches. General tooth surface loss and dentin exposure especially in mandibular incisors were detected without pain. (Figure 1)Abfraction of teeth #4 and #5 and unilateral lingual torus mandibularis in right canine/premolar area was observed (figure 2). Caries in teeth #3 #17#32 were detected. There was an amalgam filling in tooth number #5 that was not appropriate from both an aesthetic perspective and in terms of durability (figure 3). In the first visit, tooth number 7 had a metal ceramic full crown which did not match the color of the other teeth, showed metal margin exposure and an incorrect contour, all of which were noted in the smile view. Missing teeth of number #19 #20 #30, mesiolpalatal tilt of tooth number 2, mesial drift of #18 and #31 that caused insufficient space for replacement of missing teeth and also disharmonic occlusal plane was evident. Oral hygiene was appropriate but there was insufficient attached mucosa in teeth number #18 #31. All teeth had good crown root ratio in radiographic periapical view except #16. Tooth number #5 had unacceptable RCT (figure 4). VDO was evaluated and the freeway space was measured to be 4 mm (normal value is 2–4 mm) (18). Dense bone island detected as localized area of radiopacity near mesial root of tooth #18. These localized, well-defined, radiopaque lesions are asymptomatic and found more often in the mandible, especially in the molar region. Since their cause is unknown and their presence has no clinical significance, extraction of a tooth inserted into a DBI may result in an infected socket and bone resorption, therefore no specific treatment has been recommended (19). After related consultation, it was suggested that excess occlusal stress could be a contributing factor to DBI associated with the roots of the tooth, and that no treatment was indicated.For the diagnostic stage, primary impressions one-stage putty-wash (speedex coltene/switzerlan,) were made and poured by plaster (Moldano Dental Stone, Bayer Co). Centric relation was recorded by bimanual manipulation technique using acrylic anterior deprogrammer (Pattern Resin LS, GC Dental Corp) and bite registration silicone (Futar D; Kettenbach GmbH & Co) as bite registration material. The record was used for mounting the primary casts in a semi-adjustable articulator (Hanau Wide-Vue Whip Mix) by an arbitrary facebow (Hanau Springbow-Whip Mix). Posterior occlusion revealed interferences on teeth number #12, #13 and #20, #21. The possible treatment plan would be established according to investigation the space in vertical dimension at rest and occlusion and the space available for teeth restorations. Based on speech, smile evaluation and amount of restorative space in CR position it was decided to rehabilitate the dentition in the existing VDO. As a result, VDO was considered in CR at the interference point, which was approximately a 0.5 mm opening in the posterior segment and a 1 mm increase in the anterior one. Wax-up for lower anterior teeth was carried out after determination of mandibular canine level at the corner of the resting lips, followed by upper anterior teeth waxing. The quality and correctness of wax-up were verified by chairside mock-up (temporary crown and bridge material, master-dent, USA) in the mouth during phonetics, smile, and rest position. Then occlusal plane was determined using a Broadrick occlusal plane analyzer and that was verified in mouth in centric occlusion and eccentric movements. It is important to mention that mutually protection occlusal scheme was considered. Based on occlusal plane, inserting implant to replace teeth #3 and #15, RCT for teeth #8 #24 #25 #26, re-RCT of #5, crown lengthening of maxillary and mandibular anterior segment (from canine to canine), full crown of #4 #6 #8 #11, post and core crown #5 #23 #24 #25, fixed partial denture #18 #19 #20 and #29 #30 #31, porcelain laminate veneers of #7 #9 #10 #23 and occlusal veneers #12 #32 were decided.Once the treatment plan was accepted, provisional restorations were made using temporary crown and bridge material (master-dent, USA) for treatment sessions until the teeth preparation were finalized and printed temporary restorations were prepared. After scaling and root planning, caries removal was done and teeth were filled with composite (3M™ Filtek™ Z350 XT Universal Restorative/ USA). Crown lengthening stent for both jaws were made and gingival leveling in anterior segments of maxillary and mandibular arch was done in one session. Implant insertion was carried out using a semi-guided surgical guide (radiographic stent converted to surgical stent) in location of teeth number #3 (Ø 4.8mm RN, SLA® 8mm Straumann® Dental Implant System), #15 (Ø 4.8mm RN, SLA® 12mm Straumann® Dental Implant System) (figure 5). Fabrication of post resin pattern according to affirmed occlusal plane by index was done. Nickel-chrome casting post was cemented by Glass ionomer luting cement (GC Fuji I®Enhanced America).Preparation was done in this way: circumferential radial shoulder finish line was prepared for FPDs and crowns, light chamfer for laminates and conventional design (planar straight bevel) was considered for occlusal veneers.Impressions for temporary restorations were taken (Betasil Vario Putty Soft Muller Germany/Betasil Vario Light Body Muller Germany); CR registration according to past method and facebow transfer & mounting was done. After abutment selection (straight and angled tissue level regular neck), temporary restorations design was done in Exocad DentalCAD software, then they were printed (DigiDent Lite 4K, IRAN) by PMMA material shade A2 (kucco-koul, China).In try-in session, smile view, occlusal plane and occlusal contacts were assessed during CR and eccentric movements, and canine guidance and mutually protected occlusion was established. After assessing occlusion, marginal fitness and phonetic, impression making from temporary restorations & making Casts were done. Protrusive record for determining condylar inclination (R:30, L:26) and bennet angle (R:16, L:15) was completed and final impression from temporary restorations was taken. One stage putty-wash (speedex coltene/switzerlan,) and customized occlusal table were prepared. Then, final Impression was made in the same way mentioned before. Casts were mounted by cross mount technique (every other mounting procedure), cores were designed using Exocad software, then frameworks were milled IPS e.max®ZirCAD (Ivoclar Vivadent,Germany) for PFZ crowns and IPS Empress CAD( Ivoclar Vivadent , Germany) for PLV and occlusal veneers.Next, occlusal veneers were checked in mouth and radiographies were taken to check the marginal integrity. The porcelain was then applied to the frames (according to the manufacturer’s instructions) and a porcelain try-in session was conducted. After confirming restorations aesthetic and contours, final glaze and delivery was done.In the delivery session, laminates were cemented by Choice 2 Veneer Cement (BISCO Dental, USA). Dual-cure resin cement (Panavia V5, Kuraray Co) was used for occlusal veneers, full coverage restorations cemented by glass ionomer cement (Fuji II, GC Dental Corp), for implant restorations abutments were torqued to 35N according to manufacturer instruction and temp bond (NE kerr S.R.I. Scafatia, Italia) was used (figure 6,7,8,9).After delivery of restorations, oral hygiene instructions using water jet and super floss was explained for the patient, and follow-up sessions were set for 1, 6, and 12 months later, and annually afterward. After that an impression (Alginate, Chromogel) was taken for making occlusal dual splint. Delivery of occlusal splint was done in next session.DISCUSSIONThe case that was presented focused on the treatment procedure of a patient suffered from progressive wear and parafunctional habits.The challenges in this specific case were anterior deep bite, severe worn teeth, the need of esthetic and functional rehabilitation in the existing vertical dimension due to patient‘s intolerance of increasing VD and also the resultant interference of elongated maxillary incisors following with phonetics and lower smile line. It is also challenging to achieve good alignment and occlusal harmony within abutments that have different natures (tooth abutments and implant abutments) simultaneously in full mouth rehabilitation with dental implants. Moreover, material selection is a critical factor that needs special attention in worn dentitions since minimal preparation must be performed on the teeth, as well as materials that have sufficient strength in a low thickness must be chosen.Another challenge was the need to rehabilitate some areas by implant prostheses due to the reported potential failure risk of implant prostheses because of occlusal overload (20-22); however, few researchers have assessed the impact of bruxism on dental implant outcome, and the results obtained are contradictory (22-24). At present, there are some expert opinions and cautionary approaches that should be considered in order to minimize the risk of implant failure in cases of bruxism (22). In this case, zirconia crown was selected for rehabilitating due to its superior esthetics and wear resistance (25). Based on studies, an appropriate occlusal scheme (Canine-guided occlusal concept to reduce occlusal forces during jaw movement) was selected and stable contacts and an equal distribution of forces were established (22, 26).It is obvious that the loss and wear of the posterior teeth will cause a deeper overbite (27).There are several options for gaining space necessary for restorations in these patients who have attrition combined with a deep bite, including restorative dentistry, orthodontics, and oral surgery.Dawson recommended the following methods for correcting deep bites: 1. Reshaping of anterior teeth as needed in mild cases 2. Orthodontics 3. Restorative procedures 4. Surgery (5). There are some cases in which increasing VDO is considered to provide enough space for restorations and to reduce anterior overbite. An alteration in VDO may cause adaptable reactions in the temporomandibular joint (TMJ), periodontium, and occlusal morphology (28). In contrast, previous studies have reported that increasing VDO during restorative procedures could be harmful to patients, disrupting their dental physiology and adaptability (29, 30). Hyperactivity of the masticatory muscles, elevation in occlusal forces, bruxism, and temporomandibular disorders (TMDs) are reported as consequences of increasing the VDO from the literature reviews (26, 27, 31). The VDO should not be increased in cases such as full occlusal rehabilitation where restorative space can be created by crown lengthening or reshaping the teeth (31). In the present case, after apace analyzing, gaining space by crown lengthening and restorations was done.The most important goal of treatment is to form stable occlusal contact in centric relation. The concept of minimally invasive dentistry in appropriate cases preserves dentitions and supporting structures; it has also positive effects on patients’ attitude who are impressed by conservative approaches (28). Consequently, in this case, stable occlusal contacts were provided for some intact teeth (#2, #13, #14, #17) since they were in appropriate contour and position. It was decided to prepare lithium disilicate laminates as thin as possible (0.3-0.5 mm) for teeth (#7, #9, #10, #23). Occlusal veneers, which are considered minimally invasive procedures, were considered for teeth # 12 and # 28. Ceramic occlusal veneers are also known for their superior abrasion and wear resistance, biocompatibility, color stability, and low amount of preparation needed, which is confined to 1 mm (24). Planar straight bevel occlusal veneer preparation was considered for occlusal veneers in light of its desirable fracture resistance, decrease in the amount of enamel reduction, favorable fracture load, and lowest maximum principal stress (29, 30).Finally, the patient’s chief complaints were effectively resolved, and he was satisfied with the functional and aesthetic outcomes of his treatment. After 2 years, no evidence of bone loss or loss of VDO and no signs of TMD were noted. The restorations had no signs of chipping or wear, and all the surfaces were smooth.CONCLUSIONFull-mouth rehabilitation requires the proper interdisciplinary concepts to achieve acceptable functional and aesthetic results. It is important to note that the present case report emphasized the steps and phases of the treatment process as well as the use of existing VDO for meeting the biologic, restorative, and esthetic requirements.Data AvailabilityThe data used to support the findings of this study are available from the corresponding author upon request.Conflicts of InterestThe authors have no conflict of interest in this study.Author ContributionsNY: prosthodontic treatment of patient, wrote the manuscriptAM: prosthodontic treatment of patient, study conception and designSB: study conception and design, wrote the manuscriptReferences:1. Warreth A, Abuhijleh E, Almaghribi MA, Mahwal G, Ashawish A. Tooth surface loss: A review of literature. The Saudi dental journal. 2020;32(2):53-60.2. Litonjua LA, Andreana S, Bush PJ, Cohen RE. Tooth wear: attrition, erosion, and abrasion. Quintessence international. 2003;34(6).3. Davies S, Gray R, Qualtrough A. Management of tooth surface loss. British dental journal. 2002;192(1):11-23.4. Dzakovich JJ, Oslak RR. In vitro reproduction of noncarious cervical lesions. The Journal of prosthetic dentistry. 2008;100(1):1-10.5. Dawson PE. Functional occlusion: from TMJ to smile design: Elsevier Health Sciences; 2006.6. Rostiny R. The correction of occlusal vertical dimension on tooth wear. Dental Journal (Majalah Kedokteran Gigi). 2007;40(4):161-4.7. Hasanzade M, Ghodsi S, Yaghoobi N. Rehabilitation of a deep bite patient with worn dentition using minimally invasive approach: A 3‐year follow‐up. Clinical Case Reports. 2021;9(11):e05121.8. Davies S. Malocclusion–a term in need of dropping or redefinition? British Dental Journal. 2007;202(9):519-20.9. Azouzi I, Kalghoun I, Hadyaoui D, Harzallah B, Cherif M. Principles and quidelines for manaqing tooth wear: a review. Int Med Care [Internet]. 2018;2(1):1-9.10. Huang GJ, Bates SB, Ehlert AA, Whiting DP, Chen SS-H, Bollen A-M. Stability of deep-bite correction: A systematic review. Journal of the World federation of orthodontists. 2012;1(3):e89-e96.11. Gopi Chander N, Venkat R. An appraisal on increasing the occlusal vertical dimension in full occlusal rehabilitation and its outcome. The Journal of Indian Prosthodontic Society. 2011;11(2):77-81.12. Beddis H, Durey K, Alhilou A, Chan M. The restorative management of the deep overbite. British Dental Journal. 2014;217(9):509-15.13. Chabouis HF, Faugeron VS, Attal J-P. Clinical efficacy of composite versus ceramic inlays and onlays: a systematic review. Dental materials. 2013;29(12):1209-18.14. Moreira A, Freitas F, Marques D, Caramês J. Aesthetic rehabilitation of a patient with bruxism using ceramic veneers and overlays combined with four-point monolithic zirconia crowns for occlusal stabilization: a 4-year follow-up. Case reports in dentistry. 2019;2019.15. Fradeani M, Barducci G, Bacherini L, Brennan M. Esthetic rehabilitation of a severely worn dentition with minimally invasive prosthetic procedures (MIPP). International Journal of Periodontics & Restorative Dentistry. 2012;32(2).16. Mainjot AKJ. The One step‐No prep technique: A straightforward and minimally invasive approach for full‐mouth rehabilitation of worn dentition using polymer‐infiltrated ceramic network (PICN) CAD‐CAM prostheses. Journal of Esthetic and Restorative Dentistry. 2020;32(2):141-9.17. Oudkerk J, Eldafrawy M, Bekaert S, Grenade C, Vanheusden A, Mainjot A. The one-step no-prep approach for full-mouth rehabilitation of worn dentition using PICN CAD-CAM restorations: 2-yr results of a prospective clinical study. Journal of dentistry. 2020;92:103245.18. Al-Omiri MK, Lamey P-J, Clifford T. Impact of tooth wear on daily living. International Journal of Prosthodontics. 2006;19(6).19. Applebaum AJ, Lichtenthal WG, Pessin HA, Radomski JN, Simay Gökbayrak N, Katz AM, et al. Factors associated with attrition from a randomized controlled trial of meaning‐centered group psychotherapy for patients with advanced cancer. Psycho‐Oncology. 2012;21(11):1195-204.20. Nascimento MM, Dilbone DA, Pereira PN, Duarte WR, Geraldeli S, Delgado AJ. Abfraction lesions: etiology, diagnosis, and treatment options. Clinical, cosmetic and investigational dentistry. 2016;8:79.21. Li Q, Jepsen S, Albers H-K, Eberhard J. Flowable materials as an intermediate layer could improve the marginal and internal adaptation of composite restorations in Class-V-cavities. Dental Materials. 2006;22(3):250-7.22. Fruits TJ, VanBrunt CL, Khajotia SS, Duncanson MG. Effect of cyclical lateral forces on microleakage in cervical resin composite restorations. Quintessence international. 2002;33(3).23. Peumans M, De Munck J, Van Landuyt K, Kanumilli P, Yoshida Y, Inoue S, et al. Restoring cervical lesions with flexible composites. Dental materials. 2007;23(6):749-54.24. Marus R. Esthetic and predictable treatment of abfraction lesions. Inside Dentistry. 2011;7(6).25. Carlsson GE, Egermark I, Magnusson T. Predictors of bruxism, other oral parafunctions, and tooth wear over a 20-year follow-up period. Journal of orofacial pain. 2003;17(1).26. Komiyama O, Lobbezoo F, De Laat A, Iida T, Kitagawa T, Murakami H, et al. Clinical management of implant prostheses in patients with bruxism. International journal of biomaterials. 2012;2012.27. Naert I, Duyck J, Vandamme K. Occlusal overload and bone/implant loss. Clinical oral implants research. 2012;23:95-107.28. Sadowsky SJ. Occlusal overload with dental implants: a review. International journal of implant dentistry. 2019;5(1):1-5.29. Brägger U, Aeschlimann S, Bürgin W, Hämmerle CH, Lang NP. Biological and technical complications and failures with fixed partial dentures (FPD) on implants and teeth after four to five years of function. Clinical oral implants research. 2001;12(1):26-34.30. Engel E, Gomez-Roman G, Axmann-Krcmar D. Effect of occlusal wear on bone loss and Periotest value of dental implants. International Journal of Prosthodontics. 2001;14(5).31. Egbert JS, Johnson AC, Tantbirojn D, Versluis A. Fracture strength of ultrathin occlusal veneer restorations made from CAD/CAM composite or hybrid ceramic materials. Oral Science International. 2015;12(2):53-8.FiguresFigure 1. Intraoral frontal view.Figure 2. Mandibular occlusal view.Figure 3. Maxillary occlusal view.Figure 4. Initial panoramic view.Figure 5. Panoramic view after implant surgeryFigure 6. Intraoral frontal view after cementation.Figure 7. Mandibular occlusal view after cementation.Figure 8. Maxillary occlusal view after cementation.Figure 9. Final panoramic viewFigure 1

Title: Acute valve malfunction with thrombosed bioprosthetic valve after surgical aortic valve replacementAuthor name: Hiroki Moriuchi, Masaaki Koide, Yoshifumi Kunii, Takuya Maeda, Risa ShimboriAffiliations: SeireiHamamatsu Hospotal, Department of cardiovascular surgeryKey words: thrombus, bioprosthetic aortic valveCorresponding author’s address: 2-12-12, Sumiyoshi, Nakaku, Hamamatsu, Shizuoka, JapanEmail: [email protected] CONTRIBUTIONSMasaaki Koide and Takuya Maeda involved in review and editing.ACKNOWLEDGEMENTSI appreciate Mr. Andrew for reviewing manuscript and Yuki Moriuchi for total support.FUNDING INFORMATIONNoneCONFLICT OF INTEREST STATEMENTThe authors report no conflict of interest.DATA AVAILABILITY STATEMENTNoneCONSENT STATEMENTWritten informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy.CASE PRESENTATIONA 74-year-old man with chest pain was diagnosed with Stanford A acute aortic dissection and severe aortic regurgitation. Aortic valve replacement with a 21mm INSPIRIS (Edwards Lifesciences, Irvine, CA, USA) and ascending aortic replacement with 26mm J Graft (Japan Lifeline, Tokyo) was performed. Anticoagulation therapy using heparin and warfarin was started immediately. Postoperative Computed tomography(CT) revealed thrombus formation to all leaflets of the implanted valve(Figure1) and echocardiography revealed restricted leaflet motion, so surgical thrombectomy was performed. Abundant fresh thrombi adhered to all leaflets of the bioprosthetic valve, and those thrombi were carefully removed (Figure2). No damage or macroscopic degeneration on the leaflets were seen, so the implanted valve was preserved. We initiated argatoroban for 1 week, followed by aspirin and warfarin and postoperative CT showed no sign of thrombus. (Figure 3).We previously reported leaflet and coronary stent thrombosis after TAVR2, but acute bioprosthetic valve thrombosis after SAVR is extremely rare.1 Reference1. Cahill TJ, Khalique OK, Geourge Im et al. Valve thrombosis after transcatheter and surgical aortic valve replacement: Incidence and outcomes. J Thorac Cardiovasc Surg. 2022 Apr;163(4):1309-1315.2. Satoshi O, Masaaki K, Yoshifumi K, et al. Leaflet and coronary stent thrombosis after transcatheter aortic valve implantation treated by aortic valve replacement. Eur Heart J Cardiovasc Imaging. 2020 Mar 1;21(3):347Figure legendsFigure1: Computed tomography(CT) shows thrombi in all leafletsFigure2: All thrombi were removed completelyFigure3: Postoperative CT shows no thrombus in bioprosthetic aortic valveKey Clinical MessageAcute valve thrombosis after bioprosthetic aortic valve replacement even under appropriate anticoagulation therapy is extremely rare. Cardiac CT is a powerful imaging tool to detect valve thrombosis after both TAVR and SAVR.

Brief report:

Key clinical messageGallbladder (GB) neuroendocrine carcinoma (NEC) is rare and has poor prognosis. Furthermore, there is no consensus on treatment of GB-NEC.Here, we report a case of GB-NEC for which nivolumab was effective.Key word: Gallbladder NEC, immune checkpoint inhibitors, EUS-FNA