Multiple re-entry circuits may operate simultaneously in the atria in the form of dual loop re-entry using a common isthmus, or multiple re-entrant loops without a common isthmus. When two or more re-entrant circuits coexist, ablation of an individual isthmus may lead to a seamless transition  to a second rhythm, and the isthmus block can go unnoticed.We hypothesize and subsequently illustrate in three patient cases, methods to rapidly identify a transition in the rhythm and isthmus block using local electrogram changes at the ablation site.Local activation sequence changes, electrogram timing, and the behaviour of pre-existing double potentials can reveal isthmus block promptly when rhythm transitions occur during ablation of multiloop re-entry tachycardias. Multiloop atrial tachycardias may exist in the form of figure of eight re-entry with a common isthmus or individual simultaneous re-entries without a common isthmus.During multiloop atrial re-entry tachycardias, ablation of a non-common isthmus (NCI) can lead to unrecognized isthmus block and rhythm change.Local activation sequence changes, electrogram timing, and the behaviour of pre-existing double potentials can instantaneously identify block at an NCI during complex atrial flutter ablation.Prompt recognition of the local electrogram changes indicating block can help avoid unnecessary continued ablations at an already blocked isthmus and potentially add to procedural safety.Multiple re-entry circuits may operate simultaneously in the atria in the form of dual loop re-entry using a common isthmus, or multiple re-entrant loops without a common isthmus. When two or more re-entrant circuits coexist, ablation of an individual isthmus may lead to a seamless transition  to a second rhythm, and the isthmus block can go unnoticed. It is important to recognize an isthmus block promptly to avoid prolonged unnecessary ablations at an already blocked site. Electroanatomic remapping of the entire circuit to identify rhythm changes is time consuming and difficult to do frequently. Repeat entrainment mapping could be challenging due to difficulty with capture thresholds and decremental conduction in areas of scar. We describe methods to rapidly identify a transition in the rhythm using local electrogram changes at the ablation site.Figure 1). When two simultaneous circuits are operative, the rhythm can be a figure of eight  re-entry1 involving a common isthmus (CI)  or two independent re-entrant circuits with separate isthmuses . Even in a dual loop re-entry, there may be additional independent isthmuses that are unique only to one of the re-entrant loops [non-common isthmus (NCI)]. Ablation of the common isthmus will result in termination of a dual loop re-entry, whereas ablation of the NCI would result in local block and transition of the rhythm to the second re-entry.2 We hypothesized that when conduction block occurs at a NCI, the re-entry circuit would change with alteration of local activation at the site. The following would indicate rhythm change and isthmus block:In a re-entrant circuit, the local electrograms at an isthmus may be considered in terms of the depolarization wavefront approaching the site  and the wavefront receding from the site  : Merging of pre-existing DPs.Figure 1). In the case of two rhythms without a common isthmus, ablation of an individual isthmus could lead to change of activation on the Rwf and Awf . The exact changes would depend on the location and direction of activation from the second re-entry, and the nature and location of the isthmus. Finally, re-entry around a defined scar typically features wide double potentials (DPs) due to temporal separation of activation wavefronts on either side of the line of block. Merging of these DPs during ablation denotes change of activation at the site and isthmus block. Three representative cases presented below demonstrate these principles. Supplemental files are provided including video propagation maps and complete lesion sets of the three cases, and procedural details of Case 1.Any of these changes would indicate that the direction of activation at the isthmus being ablated has changed. Change in the direction of activation implies a change in the rhythm, most likely a result of isthmus block at the site of ablation. In the case of a dual loop re-entry, block at the NCI will lead to reversal of activation only at the Rwf . Ablation lesions between left and right superior pulmonary veins posteriorly (roof line) led to a 10 ms slowing of the TCL (230–240 ms). Surface ECG and coronary sinus activations remained unchanged . It was unclear if the roof line blocked or whether the small increase in TCL was due to conduction delay. The activation sequence at the Rwf was continuously being evaluated during ablation with a multipolar catheter , and a reversal of the activation wavefront was noted coinciding with the TCL change . This reflected a change in rhythm and block across the roof line. The mitral activation was delayed by 10 ms because the roof re-entry was the faster loop in this case. However, the reversal of activation at the Rwf would have been indicative of rhythm change and isthmus block even without TCL change. Further electroanatomic mapping confirmed a counterclockwise mitral flutter with no further roof re-entry . A mitral isthmus ablation between the left inferior pulmonary vein and mitral valve terminated the tachycardia and differential pacing at the roof and mitral lines indicated block at both sites.A 72-year-old man presented with recurrent atypical flutter after previous pulmonary vein isolation and typical cavo-tricuspid isthmus (CTI)-dependent flutter ablations. Electroanatomic mapping of the presenting rhythm showed dual loop re-entry with counterclockwise mitral re-entry and roof-dependent re-entry around the left pulmonary veins . The TCL was 285 ms, and wide DPs were apparent with blue isochrones adjacent to white isochrones at the mid part of the scar. No simultaneous re-entry was noted around the tricuspid valve (TV), but a potential lower loop clockwise re-entry around the inferior vena cava was noted. An ablation line was performed from TV to the atriotomy scar. No tachycardia termination, change in TCL, change in coronary sinus (CS) activation, or change in surface ECG occurred despite anatomic completion of the ablation line. However, the wide DPs seen previously at the atriotomy site were no longer seen and replaced by closely spaced electrograms . Conversion of DPs to closely spaced electrogram was interpreted as indicative of a rhythm change and block of the isthmus being ablated. Additionally, the Rwf electrogram advanced (blue to red isochrone) and Awf electrogram advanced (blue to orange isochrone), both indicating a rhythm change. Remapping of the rhythm was undertaken revealing no further scar re-entry but continued lower loop re-entry around the inferior vena cava . A CTI ablation terminated the lower loop re-entry.A 52-year-old man with previous history of atrial septal defect (ASD) repair presented with ECG morphology suggestive of typical CTI flutter. Electroanatomic mapping revealed re-entry around an atriotomy scar anterior to the SVC  without change in TCL, ECG morphology, or CS activation. The timing of the first component of the DP was the same as previous electrograms at the site while the second component was delayed either from block or conduction delay at the site. Further electroanatomic mapping was not undertaken and completion of the CTI ablation posterior to the scar (common isthmus) terminated the tachycardia. Bidirectional CTI block was confirmed.A 74-year-old man presented for ablation of typical CTI flutter and 3D electroanatomic map demonstrated dual loop re-entry with counterclockwise typical flutter and intra-isthmus re-entry around a scar mid-way in the CTI. The common isthmus of the dual loop was the part of the CTI posterior to the scar and the NCI was the part of the CTI anterior to the scar. Ablation was started at the TV end of the CTI, and wide DP formation was noted during ablation of the CTI anterior to the scar , the Rwf activation is reversed from the initial pattern, but the rest of the left atrial activation remained unchanged from the mitral re-entry. A reversal of activation can be identified with either a multipolar mapping catheter instantaneously (as we did in Case 1) or using the roving ablation tip to map a limited area at the Rwf. When a stable multipolar mapping catheter position at the Rwf area is difficult, the catheter may be moved to the area as needed to observe electrogram sequence and timing. The ablation tip electrograms provide a continuous guide for electrogram timing changes at Rwf or Awf areas. If high density mapping of the initial rhythm has been undertaken, one can predict the area where Rwf activation reversal would occur from the line of collision of activation wavefronts during the original dual loop re-entry.2 In Case 1, one could predict that the Rwf electrogram timing will change to immediately past the reference  from before the reference  when block occurs. Here, one can watch for the Rwf electrograms delaying to the blue isochrone during ablation as likely indicative of block. The timing of the Awf remains unchanged in Case 1 despite the increase in TCL because the CS (reference electrode) activation delays equally and the relative timing of electrograms are unaffected.In this report, we characterize methods for quick identification of rhythm change and isthmus block during ablation of complex atrial flutters. We propose that conduction block at an NCI during multiloop re-entry would result in identifiable activation changes at the site. Figure 2). The exact changes vary depending on the relative locations of the circuits and isthmuses. Reversal of activation of the Rwf is expected if the isthmus is anatomically confined because this area will now be activated from a different wavefront in the opposite direction. If the area is not confined, reversal of activation may not occur, but the timing may advance or delay . In addition to the Rwf activation changes, the Awf activation could also change here. These changes are demonstrated in patient Case 2. Any change (advancement or delay) of the Awf electrogram would indicate rhythm change because ablation of the isthmus should not affect the activation of areas temporally preceding it unless the area is activated differently. It is not necessary to demonstrate activation reversal when changes occur in the Awf—one can use a single electrogram, and advancement or delay would be sufficient to show rhythm change. Similarly, any advancement of Rwf electrograms will also indicate a rhythm change because ablation induced slowing of conduction can only delay the Rwf electrograms. The scar re-entry in Case 2 also illustrates the usefulness of observing DP timing. Merging of the DP electrogram along the scar indicates termination of the re-entry around the scar and a rhythm change. A comparison with Case 3 illustrates the difference between DP merging vs. DP formation during ablation. The former, when confirmed along the scar, indicates rhythm change, whereas the latter can be rhythm change or conduction slowing. It should be noted that rhythm change during ablation of an isthmus could also occur with revelation of a re-entrant circuit or a focal tachycardia that was not apparent before. The activation changes we describe here are applicable to occurrence of such unexpected new rhythms.In the case of two re-entrant circuits without a common isthmus, block in one isthmus transitions the rhythm to the second re-entry (While the local electrogram changes we describe here should prompt the electrophysiologist to re-evaluate the need for continued ablation at the site, it should be used as a guide rather than definitive evidence of isthmus block. Achievement of block does not mean that the ablation at the site should be immediately discontinued. There may be value for further ablation and completion of the anatomic line depending on the stage of ablation. While the changes at the Rwf perhaps provides the most information during an ablation, reversal of Rwf activation may not always indicate block at an isthmus. Significant delay with Rwf reversal can occur due to focal breakthrough conduction on the ablation line or epicardial conduction with breakthrough distant from the line of ablation. Ultimately, Rwf reversal should be taken as likely to indicate block and the state of isthmus conduction further confirmed after rhythm termination.Local activation sequence changes, electrogram timing and the behaviour of pre-existing DPs can detect isthmus block when rhythm transitions occur during ablation of multiloop re-entry tachycardias. Expeditious identification of isthmus block, that otherwise may have gone unnoticed, could improve patient safety and outcomes.euac161_Supplementary_DataClick here for additional data file.


Hypoinsulinemia is a pathological consequence of diabetes mellitus that can cause a number of complications of the central and peripheral nervous system. Dysfunction of signaling cascades of insulin receptors under insulin deficiency can contribute to the development of cognitive disorders associated with impaired synaptic plasticity properties. Earlier we have shown that hypoinsulinemia causes a shift of short-term plasticity in glutamatergic hippocampal synapses from facilitation to depression and apparently involves mechanisms of glutamate release probability reduction. Here we used the whole cell patch-clamp recording of evoked glutamatergic excitatory postsynaptic currents (eEPSCs) and the method of local extracellular electrical stimulation of a single presynaptic axon to investigate the effect of insulin (100 nM) on the paired-pulse plasticity at glutamatergic synapses of cultured hippocampal neurons under hypoinsulinemia. Our data indicate that under normoinsulinemia additional insulin enhances the paired-pulse facilitation (PPF) of eEPSCs in hippocampal neurons by stimulating the glutamate release in their synapses. Under hypoinsulinemia, insulin did not have a significant effect on the parameters of paired-pulse plasticity on neurons of PPF subgroup, which may indicate the development of insulin resistance, while the effect of insulin on PPD neurons indicates its ability to recover the form normoinsulinemia, including the increasing probability of plasticity to the control level in of glutamate release in their synapses. Hypoinsulinemia is one of the diabetic syndromes and causes a number of complications of the central and peripheral nervous system functioning. Under type 1 diabetes mellitus this condition can manifest itself by decreased production of insulin by pancreatic β-cells caused by their massive death, and under type 2 diabetes mellitus following overstimulation of the insulin secretory machinery of the β -cell for compensation of permanent hyperglycemia. The brain is a highly insulin-sensitive organ  with higRecently much attention has been devoted to the role of insulin-dependent signaling in the regulation of neurogenesis and synaptic plasticity in the hippocampus and its effect on memory and learning processes. Various positive effects of insulin have been described, such as the neurotrophic action on both differentiated neurons and neuronal stem cells , stimulaSince hypoinsulinemia may affect the function of many insulin-sensitive organs, the primary culture of rat hippocampal neurons can be successfully used to determine the effect of insulin on the functioning of hippocampal synapses and their plasticity. Such approach allows to eliminate the numerous modulatory effects of insulin on some other organs and body systems.The role of insulin in synaptic plasticity at hippocampus has been studied earlier , howeverAll experimental procedures were performed in accordance with international principles of the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes, Strasburg, 1986; the Law of Ukraine “On protection of animals from cruelty” and approved by the Animal Care Committee of Bogomoletz Institute of Physiology.°C). Then, the hippocampal segments were washed with culturing solution containing Eagle’s modified medium (MEM) 9.6 g/l, 10% horse serum, 2.2 g/l NaHCO3, 103 nM insulin, penicillin 25 U/ml and streptomycin 25 μg/ml. The concentration of insulin for hippocampal neurons culturing was quite consistent with the physiological insulin levels, that can be found in brain tissues  hippocampal neurons were incubated in insulin-free media for 4 days . In addition, the PPR values in the PPD subgroup of hypoinsulinemia after insulin addition did not differ significantly from those measured in the control of normoinsulinemia , while control PPR values in normoinsulinemia and in the PPD subgroup of hypoinsulinemia significantly differed .To simulate hypoinsulinemia conditions, mature hippocampal cell cultures 16–20 DIV were placed into an insulin-free medium for 4 days, after that electrophysiological experiments were carried out. The experimental conditions corresponded to those described for cultures of the normoinsulinemia group. In hypoinsulinemia, glutamatergic hippocampal synapses were divided into two subgroups depending on the expression of the paired-pulse plasticity form . In the The present results are consistent with the previous data regarding presynaptic modulation of plasticity in glutamatergic synapses of hippocampal neurons under insulin action , when thm), while no significant changes of the release probability (p) were observed in these synapses. The action of insulin in this case may rather reflect its modulating effect on postsynaptic glutamate receptors and/or an increase in number of vesicles in the immediately releasable or primed pool at their presynapses. An increase of the mEPSCs frequency can also testify in favor of the latter, which is consistent with the previous reports, showing the stimulation of basal neurotransmitter release by insulin . Apparently these changes do not affect the release probability (CV of eEPSCs and p did not change under insulin action).It has been suggested that insulin may target both pre- and postsynaptic membranes to affect basal synaptic transmission. For instance, it enhances the activity of postsynaptic NMDARs (N-methyl-D-aspartate receptors) in the synaptic membrane and mediates postsynaptic effects of the hormone . On the Physiological and pathological conditions can influence insulin signaling and efficacy. For instance, patients with obesity and/or type 2 diabetes mellitus had lower insulin concentrations in the cerebrospinal fluid despite higher levels of this hormone in peripheral plasma . Obesityin vivo. It was reported that normal physiological levels of insulin in circulating blood of adult rats is 180–240 pM .MS carried out the experiments, conceived and designed the analyses, collected the data, performed the analysis, and wrote the article. OK carried out the experiments, collected the data, and performed the analysis. SF and NV contributed to the study design and article editing. All authors contributed to the article and approved the submitted version.


This review analyzes muscle activity following mandibular condylar fracture (CF), with a focus on understanding the changes in masticatory muscles and temporomandibular joint (TMJ) functioning. Materials and Methods: The review was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A search was performed on online databases using the keywords “masticatory muscles” AND (“mandibular fracture” OR “condylar fracture”). The eligibility criteria included clinical trials involving human intervention and focusing on muscle activity following a condylar fracture. Results: A total of 13 relevant studies were reviewed. Various studies evaluated muscle activity using clinical evaluation, bite force measurement, electromyography (EMG), magnetic sensors and radiological examinations to assess the impact of mandibular fractures on masticatory muscles. Conclusions: Mandibular condylar fractures can lead to significant changes in muscle activity, affecting mastication and TMJ functioning. EMG and computed tomography (CT) imaging play crucial roles in assessing muscle changes and adaptations following fractures, providing valuable information for treatment planning and post-fracture management. Further research is required to explore long-term outcomes and functional performance after oral motor rehabilitation in patients with facial fractures. Standardized classifications and treatment approaches may help improve the comparability of future studies in this field. The mandible is the second most commonly fractured part of the maxillofacial skeleton after the nasal bone due to its position and prominence. The angle 27.0%), symphysis 21.3%), body (16.8%), ramus 5.4%), and coronoid (1.0%) were the most frequently injured sites, independent of mechanism [.3%, body7.0%, sym%, and coThe relative frequency of such fractures is determined by the particular morphology of the condyle, which makes it the most fragile point of the mandibular bone ,6. On thThere are numerous classifications of CF in use internationally ,30. As aHead-condyle fracture: located at the level above or at the level of the joint capsule and according to its course can be defined as vertical or horizontal;Condylar-neck fracture: located in the area below the head of the condyle;Subcondylar fracture: located below the neck of the condyle.Thus, based on the location of the fracture they are distinguished into:Early diagnosis of CF is critical in deciding the correct treatment plan with the aim of avoiding the occurrence of subsequent complications. In case of suspected mandibular fracture, very often as a result of sustained trauma, it is necessary to proceed with an objective clinical examination based on palpation of the area, both intra-oral and extra-oral inspection, and assessment of joint function ,34. RadiFor many years, conservative therapy was considered the gold standard for the treatment of the mandibular CF . In the Muscular therapy following temporomandibular disorders caused by condyle fracture is critical for proper masticatory function recovery. It tries to restore muscle balance and enhance joint mobility with focused workouts, manual treatment, and specialized equipment . The objThe aim of this review is to analyze muscle activity following mandibular CF.This study was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and submitted to PROSPERO  with 448,110 [The search was conducted on 13 July 2023 on the PubMed, Scopus, and Web of Science databases without the inclusion of any time interval. The search approach included the following Boolean keywords: “masticatory muscles” AND (“mandibular fracture” OR “condylar fracture”). These keywords were chosen because they most accurately reflected the aim of our investigation, which was to find out more about the activity and function of the masticatory muscles following a unilateral or bilateral mandibular CF.The two steps of the selection process were the appraisal of the title and abstract and the complete text. Any article that fit the following requirements was taken into consideration: (a) clinical trials including human intervention; (b) muscle activity following a condylar fracture; (c) free full text. Publications  that lacked original data were not included. Titles and abstracts from the preliminary search were retrieved and evaluated for relevance. Full articles from pertinent research were acquired for further analysis. The retrieved studies were assessed for inclusion using the aforementioned criteria by two different reviewers (R.M. and A.P.).R.M. and A.P., the two reviewers, independently evaluated the quality of the studies, based on selection criteria after performing a database search to extrapolate the findings. In order to use with Zotero, the chosen articles were downloaded in the 6.0.15 version. A senior reviewer (F.I.) was consulted in order to address any disagreements between the two reviewers.The PICOS  criteria, which are used in this evaluation, encompass population, intervention, comparison, outcomes, and study design .The quality of the included papers was assessed by two reviewers, RF and EI, using the reputable Cochrane risk-of-bias assessment for randomized trials (RoB 2). The following six areas of possible bias are evaluated by this tool: random sequence generation, allocation concealment, participant and staff blinding, outcome assessment blinding, inadequate outcome data, and selective reporting. A third reviewer (FI) was consulted in the event of a disagreement until an agreement was reached.A total of 485 publications were found in the online database ; no papers were found using a manual search. After 259 duplicate studies were removed, 226 studies were evaluated by looking at the title and abstract. From here, 37 records were chosen out of 189 items that failed to fulfill the requirements for inclusion. Subsequently, 21 non-retrieved records were excluded. There were 16 reports evaluated for eligibility, and three reports were removed. In the end, 13 studies were reviewed for the qualitative analysis. The selection process and the summary of selected records are shown in The following review analyzes a total of 13 papers including four case control (30%), four observational studies (30%), three prospective cohort studies (24%), and two retrospective studies (16%). Among the analyzed studies, three deal exclusively with bilateral fractures, five deal exclusively with unilateral fractures, and the last five consider both unilateral and bilateral fractures.The risk of bias in the included studies is reported in Following mandibular condylar fractures, alterations in masticatory muscles occur, impacting temporomandibular joint function. Assessing these changes requires comprehensive methods. Clinical palpation, bite force analysis, electromyography, CT scans, and magnetic jaw tracking are employed to scrutinize muscular alterations. These techniques offer insights into muscle functionality, symmetry, and coordination post-fracture, aiding a comprehensive understanding of post-traumatic masticatory muscle adaptations and their implications on mandibular function.Lindahl’s study proposed to understand the recovery process and the potential development of dysfunction in the masticatory system following CF. Examiners performed a comprehensive clinical examination, combined with radiographic evaluations, on a group of 67 individuals of different age groups . During Mastication is a crucial function of the stomatognathic system, and chewing force is an important parameter for assessing the restoration of function after surgery.Talwar’s study analyzes the effects of bilateral fractures of condylar processes on chewing force. Through the analysis of data from cephalograms and biomechanical studies, significant morphological and biomechanical changes were found in patients with CF . A decreIn an American study, the authors investigated whether chewing force in patients with unilateral fractures of the condylar process of the mandible varied according to the type of restorative treatment whether with open or closed techniques. Data from 155 patients with unilateral fractures of the condylar process of the mandible treated with open or closed techniques were analyzed . MaximumIn contrast, Kuntamukkula’s study evaluates the dynamic stability of the TMJ in patients with unilateral condyle fractures undergoing reduction surgery and open internal fixation. During the six-month recovery period, bite force was evaluated both statically and dynamically on both sides of the mandible . The resSalunkhe et al., also investigated significant changes in masticatory loads in patients with mandibular condyle fractures undergoing reduction surgery and open internal fixation. The results showed that, initially, the bite force in the molar region was significantly reduced in the first postoperative week, but gradually approached the levels of the control group by the ninth postoperative week . This suFractures of the mandibular condyle may temporarily affect chewing strength, but with proper surgical treatment and recovery period, chewing ability tends to improve over time.Sforza’s study aims to quantitatively assess the percentage contribution of rotation and translation movements of the mandible during maximum mouth opening in patients treated for CF . The resThe results indicated that patients showed altered patterns of mandibular motion during mouth opening, with a larger percentage of rotation and reduced vertical displacement compared to healthy individuals. EMG indices in patients also differed from those in the healthy subjects, indicating potential functional adaptations following the fractures . OverallHjorth’s study also evaluates parameters recorded through EMG: it reports the results of a longitudinal study conducted on patients with unilateral fractures of the mandibular condyle . The aimDuring observation, the level of muscle activity at rest  did not change significantly. However, there was a significant increase in muscle activity during maximal contraction of the contralateral temporalis and masseter muscles (on the side opposite the fracture) from the time immediately after fracture treatment (T0) until 6–12 months later (T2). Furthermore, during natural mastication, the maximal activity of the anterior temporalis muscle increased significantly over time .During unilateral mastication , a significant increase in activity was noted in the anterior temporalis and contralateral masseter muscles from T0 to T2. Furthermore, muscle contractions became shorter and stronger in all muscles during UM, except for the ipsilateral masseter (on the same side as the fracture), which had a significant increase in activity only between the first and second examinations .In summary, EMG revealed significant changes in muscle activity in patients with unilateral mandibular condyle fractures. Increases in the maximal muscle activity of the contralateral temporalis and masseter muscle were observed during contraction and natural chewing . FurtherPagliotto da Silva aimed to investigate the oral motor function in patients with facial fractures .The study included 38 adult patients with facial fractures, divided into two groups based on the treatment received: Group 1 (G1) received open reduction of facial fractures, and Group 2 (G2) received closed reduction with maxillomandibular fixation. A control group of 19 healthy volunteers was also recruited .The participants underwent oral motor clinical assessment, mandibular range of movement measurements, and surface electromyography (sEMG) evaluation of the anterior temporal and masseter muscles. The data were analyzed using non-parametric tests.The results showed that patients with facial fractures had poorer performance in oral motor functions, including swallowing and mastication, compared to the control group. Both G1 and G2 exhibited a limited mandibular range of motion, particularly in maximal incisor distance. The electromyographic assessment revealed that both groups of patients with facial fractures had lower overall muscle activity compared to the control group .However, there were no significant differences in oral motor function or muscle activity between G1 and G2, suggesting that the severity of facial fractures did not influence muscle function and performance four months after fracture correction.Overall, the study indicates that patients with facial fractures experience deficits in oral motor function, but the type of fracture treatment (open or closed reduction) did not significantly affect the outcomes of muscle function and performance after four months of treatment. The electromyographic evaluation of the anterior and posterior heads of the temporalis, masseter and sternocleidomastoid muscles in bicondylar fractures showed a lower activity of the masseters than that of the temporals during the closing phase, especially on the working side, the opposite of what normally happens . During A practical tool for evaluating soft tissue changes in the nervous system after a CF that is not visible on standard radiographs is CT. It has been used to determine the disc’s position and assess how well it is functioning. It has also been shown to be superior to traditional radiography in terms of detecting subtle changes in the condylar head and the mandibular fossa ,61,62. AA CT scan analysis of the masseter, temporalis and lateral pterygoid muscle showed that the first two muscles on the fractured side have a similar density to those on the non-fractured side, although slightly lower. The only statistically significant difference is related to the lower density of the lateral pterygoid muscle on the fractured side compared to the non-fractured side, considering that the lateral pterygoid has absolutely less density than the rest of the other muscles. In some cases, the muscle shows a reduction in density in direct proportion to the passage of time .Kahl-Nieke et al. analysed the changes undergone by the lateral pterygoid muscle in 19 child patients with a unilateral fracture during and after treatment with functional devices that promote condylar remodeling. The device was worn for approximately nine months and was intended to promote condyle formation with resorption of the fractured fragment. In the follow-up in more than 70% of the patients, there was a reduction in the muscle mass of the lateral pterygoid in the range of 13 to 69%. The extent of the mass reduction is directly proportional to the depth and severity of the fracture: deep fractures and fractures with complete dislocation of the disc suffered the greatest mass reduction .In patients with bilateral CF due to muscle contraction, there is an open-bite and retroposed position of the mandible. After 10 days of intermaxillary fixation, months of jaw exercises, muscle training, and mandibular manipulation, the open bite was removed. Masticatory muscle adaptation allows for the restoration of occlusion and function .Following a mandibular fracture, in addition to the alteration of the anatomy of the TMJ the function also changes: the masticatory cycles are altered, especially the changes that the two ends of the lateral pterygoid muscle undergo ,66.To assess the masticatory cycles, measurements were taken during the chewing of a gummy bear after the insertion of a small magnet at the level of the lower incisors, the patient’s face with the frankfurter plane parallel to the floor. A magnetic sensor array  was attached to the patient’s head to monitor the activity of the magnet. All these devices are connected to a computer that reports what occurs in the three planes of space ,71,72,73In the case of bicondylar fractures, the muscles affected are the two ends of the lateral pterygoid, which makes the protrusion movement difficult since it fits over the head and neck of the condyle. The other muscles are not particularly affected .The study proposed by Throckmorton hypothesizes that in unilateral CF treated with the closed technique, the alterations of the masticatory cycles persist even after bone healing, unlike what happens with the open technique .The patients were divided into two groups: the first group was treated surgically, using a retromandibular approach for surgery in the condylar area. In these patients, plates were fixed without compression using at least two screws of 2 mm length. The second group included patients who did not receive any surgical treatment of the condyle but used Class II elastics to guide the mandible into correct occlusion and favor pseudocondylar formation. Patients in both groups followed the same physiotherapy exercises and the use of rubber bands to guide correct occlusion .These patients were treated either surgically or in a combined manner  are not significantly affected by surgical treatment of unilateral condylar process fractures. On the side opposite the fracture, however, surgical treatment better normalizes opening incisor channels during mastication. Similar to the opening phases, the patients’ reduced excursion toward the working side during the fast-close phase is consistent with the inhibition of normal translation of the balancing side condyle after bilateral condylar process fractures .Heterogeneous study designs: The included studies vary in design, such as case-control, observational, retrospective, and prospective studies. Combining data from different study designs may introduce heterogeneity and affect the validity of the review’s conclusions.Limited sample sizes: Some of the included studies have small sample sizes, which could limit the statistical power and generalizability of the findings.Lack of quality assessment: The review does not mention whether a quality assessment of the included studies was conducted. Evaluating the methodological quality of the studies is essential to assess the overall reliability of the evidence.Limited scope of analysis: The review mainly focuses on muscle activity following mandibular CF, but it does not discuss other potential outcomes or complications related to these fractures, such as pain, joint function, or psychosocial impact. A more comprehensive analysis of the implications of these fractures would provide a more robust understanding of the topic.The review has several limitations:In conclusion, the systematic review of literature has revealed a multifaceted landscape of evidence regarding the impact of condylar fractures on the masticatory system and the subsequent recovery processes. Clinical palpation studies underscore the age-dependent variations in the consequences of condylar fractures, with children generally experiencing milder dysfunction compared to adolescents and adults, potentially related to persistent condylar fragment dislocation. Bite-force analyses elucidate the dynamic adaptations of the masticatory system post-fracture, with reductions in force initially observed and subsequent adjustments to protect the injured site. Electromyography studies offer insights into muscle activity changes, revealing muscular adaptations and functional alterations, particularly in patients with unilateral fractures. CT scans provide valuable insights into soft tissue changes and muscular atrophy, emphasizing the importance of long-term evaluation. Magnetic jaw track device studies shed light on altered masticatory cycles following fractures, with differences observed between surgical and non-surgical treatments.Overall, these findings underscore the complexity of the masticatory system’s response to condylar fractures and the importance of tailored treatment approaches and long-term monitoring for optimal recovery. Further research is needed to enhance our understanding of these processes and to guide more effective clinical management strategies for patients with mandibular condylar fractures.


A novel approach is presented in this study for the classification of lower limb disorders, with a specific emphasis on the knee, hip, and ankle. The research employs gait analysis and the extraction of PoseNet features from video data in order to effectively identify and categorize these disorders. The PoseNet algorithm facilitates the extraction of key body joint movements and positions from videos in a non-invasive and user-friendly manner, thereby offering a comprehensive representation of lower limb movements. The features that are extracted are subsequently standardized and employed as inputs for a range of machine learning algorithms, such as Random Forest, Extra Tree Classifier, Multilayer Perceptron, Artificial Neural Networks, and Convolutional Neural Networks. The models undergo training and testing processes using a dataset consisting of 174 real patients and normal individuals collected at the Tehsil Headquarter Hospital Sadiq Abad. The evaluation of their performance is conducted through the utilization of K-fold cross-validation. The findings exhibit a notable level of accuracy and precision in the classification of various lower limb disorders. Notably, the Artificial Neural Networks model achieves the highest accuracy rate of 98.84%. The proposed methodology exhibits potential in enhancing the diagnosis and treatment planning of lower limb disorders. It presents a non-invasive and efficient method of analyzing gait patterns and identifying particular conditions. Lower extremity disorders have been identified as a significant factor contributing to disability and reduced quality of life on a global scale ,2. OsteoGait analysis is employed in a wide variety of domains, including medical diagnostics ,14,15, oPoseNet offers a non-invasive and user-friendly approach to extracting human pose data from videos, obviating the necessity for dedicated apparatus or body-attached markers. This facilitates a more authentic and unimpeded evaluation of gait patterns in real-world contexts. The application of deep learning in PoseNet enables the extraction of complicated and detailed features from videos, resulting in a comprehensive depiction of movements in the lower limbs. The characteristics effectively capture the complex variations and fluctuations in an individual’s gait, which have the potential to serve as indicators for particular disorders affecting the lower limbs. This methodology presents the potential for improved accuracy in diagnosis. The study has the following contributions.The data were collected from a total of 174 real patients and normal individuals, comprising both male and female participants. The data collection process involved capturing videos of the participants using a camera while they walked on a designated walkway at the Tehsil Headquarter (THQ) Hospital in Sadiqabad.The data were gathered by the system via video recordings, thereby obviating the necessity for intrusive sensors or apparatus affixed to the subjects’ bodies. The implementation of this data collection method that minimizes interference guarantees a more authentic and unrestrained evaluation of gait patterns, thereby enhancing the ecological validity of the system.The system employs PoseNet, a deep learning model, to extract relevant features from videos that capture movements of the lower limbs. By utilizing the features of PoseNet, the system capitalizes on the model’s capacity to accurately estimate the human pose, facilitating a thorough examination of gait patterns.Through the application of machine learning (ML) algorithms to the extracted PoseNet features, the system possesses the capability to effectively classify and distinguish various disorders that impact the hip, ankle, and knee. The implementation of automation in this context serves to decrease the level of subjectivity involved in manual analysis, while also reducing the amount of time required for such analysis. As a result, the process of diagnosis becomes more expedient and efficient.The aforementioned contributions play a significant role in the advancement of lower limb disorder classification, thereby holding the potential to yield substantial benefits for both clinical practice and research endeavors.The subsequent sections of the article are structured as follows: In recent years, there has been growing interest in the field of gait analysis and the categorization of joint abnormalities. This attention is driven by the desire to enhance the accuracy of diagnosis and treatment methods. Various studies employ ML and deep learning techniques to automatically categorize joint abnormalities using gait data. Each study in the field of gait analysis is centered around a particular condition or aspect and employs a range of methodologies and evaluation metrics. The research conducted by  centers In , the resThe aim of  was to dIn , the resPrevious research studies provide evidence of the efficacy of ML and deep learning methodologies in the automated categorization of joint abnormalities using gait data. The utilization of diverse modalities, including RGB-D cameras, 2D video, and ground reaction force measurements, exemplifies the multifaceted nature of these methodologies. Nevertheless, certain studies demonstrate limitations in terms of moderate accuracy, the necessity for supplementary evaluation metrics, and comparatively limited sample sizes. This manuscript introduces a novel approach to categorizing lower limb disorders, focusing on ankle, knee, hip, and normal subjects. The proposed method involves the utilization of PoseNet features extracted from video data. The approach centers on utilizing PoseNet, a pose estimation model based on deep learning, to extract significant features from the video recordings. The primary objective of the proposed methodology is to improve the precision and effectiveness of diagnosing lower limb disorders through the utilization of video data. This approach capitalizes on the abundance of valuable information pertaining to subjects’ movements and joint positions that can be extracted from video recordings. The application of this methodology holds promise in assisting healthcare practitioners in the identification and classification of distinct lower limb disorders, thus facilitating the implementation of suitable treatment and rehabilitation approaches.The methodology of this study was implemented on a Core i7 11th-generation machine running the Windows operating system. The proposed methodology was implemented using Jupyter Notebook , a web-bThe research methodology employed for the classification of lower limb disorders is depicted in The research was carried out in compliance with ethical protocols and received approval from the ethics committee at Khwaja Fareed University of Engineering and Technology (KFUEIT). The committee conducted a thorough evaluation of the ethical implications of the study, guaranteeing adherence to the principles delineated in the Helsinki Declaration. Through the acquisition of ethical approval, the study effectively showcased its dedication to safeguarding the well-being, entitlements, and confidentiality of the individuals engaged in the research. The data collection was conducted at the THQ Hospital located in Sadiq Abad. The data were obtained from a group of 174 individuals, ranging in age from 40 to 60 years, encompassing both male and female participants. To achieve an accurate depiction of the lower limbs’ temporal features, frames were extracted from the videos at a rate of 30 frames per second (fps). The selection of this higher frame rate was made to record the motions linked to lower limb disorders precisely. Subsequently, the frames underwent the application of the PoseNet feature extraction technique. The PoseNet algorithm is extensively employed in the estimation of the human body pose . The sysUpper Body:-Left Shoulder;-Right Shoulder;-Left Elbow;-Right Elbow;-Left Wrist;-Right Wrist;-Left Pinky;-Right Pinky;-Left Index;-Right Index;-Left Thumb;-Right Thumb.Lower Body:-Left Hip;-Right Hip;-Left Knee;-Right Knee;-Left Ankle;-Right Ankle;-Left Heel;-Right Heel;-Left Foot Index;-Right Foot Index.The mentioned landmarks were utilized as points of reference to denote the positioning of individuals within the frames of the video. The extraction of pose landmarks yielded significant data pertaining to the spatial positioning and arrangement of different body parts, such as the shoulders, elbows, wrists, hips, knees, and ankles. The accurate identification and analysis of joints and key points obtained through pose estimation play a vital role in effectively characterizing the posture and movements exhibited by individuals while walking. A widely employed method of representing pose landmarks involves the utilization of a skeletal representation. This process entails establishing connections between the pose landmarks through the use of lines, resulting in the formation of a skeletal framework that visually portrays the physical structure of the person, as illustrated in Number of key points = 22.Number of extracted features from each key point = 4.Total number of features = 22 × 4 = 88.Feature scaling plays a pivotal role in the data preprocessing phase that follows feature extraction. The primary objective of this process is to ensure that all extracted features undergo a uniform transformation in relation to their scale or range. This step holds significance due to the potential for significant variances in value ranges among different features, which can impact the performance of specific ML algorithms. Feature scaling is a technique that mitigates the disproportionate influence of features with larger magnitudes on the model training process. The standard scaler technique was utilized in this manuscript for feature scaling . The staX is the original feature value;The normalization process guarantees that the feature values are standardized, irrespective of their initial distribution, by centering them around zero and applying uniform scaling. Following the application of the standard scaler to the dataset, the subsequent step in the methodology entailed the implementation of Principal Component Analysis (PCA) on the scaled features. PCA is a statistical methodology employed to achieve dimensionality reduction . The maiThe dataset consists of a heterogeneous compilation of 1740 videos, encompassing a range of categories including hip, ankle, knee, and normal. Upon analyzing The data distribution is represented by a cubic hyperplot in The dataset was split into a training set and a testing set using a ratio of 70% and 30%, respectively, in order to compare the performance of several ML models. This partitioning facilitated the evaluation of the model’s performance on data that had not been previously observed. We used various widely used ML algorithms, including Random Forest (RF), Extra Tree Classifier (ETC), K-nearest neighbor (KNN), Adaboost, and Multilayer Perceptron (MLP), as well as deep learning models like Artificial Neural Networks (ANN) and Convolutional Neural Networks (CNN). These ML models are used in different real-time applications related to disease diagnosis , computeK-fold cross-validation was performed to assess the generalizability of the trained models. K-fold cross-validation is a technique that divides a dataset into K subgroups and trains and evaluates a model K times, once for each subset as a validation set, to analyze and improve the model’s performance and generalization . In thisThe data presented in The confusion matrix presented in This study examined the computational time complexities associated with classifiers used for the classification of lower limb disorders using video data. The analysis of computational complexity was conducted with a focus on the hyperparameters that resulted in higher accuracy. The experiments were performed using an HP ProBook 450 G4 laptop equipped with 16 GB of RAM and an Intel Core i5 7th generation processor. The findings in The MLP stands out as a strong competitor in light of the performance metrics and computational time complexity. The MLP demonstrates superior performance in terms of accuracy, precision, recall, and F1-score while exhibiting a comparatively lower level of computational time complexity. The ANN and CNN also exhibit exceptional performance; however, their computational time complexities are comparatively higher than those of the MLP.The primary objective of the proposed study was to categorize lower limb disorders by utilizing PoseNet features that were extracted from video data. The findings of the study demonstrate a high level of encouragement, as evidenced by the attained accuracy rate of 98.8% and the cross-validation score of 99%. These results highlight the potential of the proposed method in achieving precise classification. Upon comparing the current study with previous research conducted on knee osteoarthritis  and gaitThis research introduces a novel method of classifying lower limb problems based on gait analysis and PoseNet features, with an emphasis on the knee, hip, and ankle. To obtain detailed information about the bio-mechanics of the lower limb, PoseNet is used to extract important body joint movements and positions from video footage in a non-invasive manner. After feature extraction and feature engineering, several machine and deep learning models were trained and tested on the dataset. The results show that the suggested method is highly accurate and precise in the classification of lower limb diseases, with accuracies ranging from 93.44% to 98.84%. Non-invasiveness, user friendliness, and the ability to capture natural gait patterns are just a few of the benefits of this method. It has the potential to help medical personnel to effectively identify and precisely diagnose lower limb disorders, allowing for targeted treatment and rehabilitation techniques. Several directions could be taken by researchers in the future. First, improving the models’ applicability would require an increase in the size and diversity of the dataset. The validity and clinical utility of this technique could be further confirmed by exploring its application to various illnesses and conditions affecting the lower limbs.


However, the MiECCsystem is a closed-loop system, employing kinetically assisted venous drainage, whichmay increase the risk of introducing venous air. Venous air travels easily through abypass system resulting in gaseous microemboli in the arterial line prior to enteringthe patient’s arterial circulation. The number of cerebral microemboli increases inconventional ECC systems during drug bolus injections, blood sampling, low blood volumelevels in the venous reservoir, and infusions. Microemboli activate the inflammatory response and may evenobstruct the blood flow in the capillary vessels, causing ischemia of thetissues. Consequently, thesepathophysiological processes may lead to a decline in the cognitive function of thepatient. Less microemboli were detected in the arterial line and in the cerebral vesselsduring the use of MiECC systems as compared to conventional systems. However, morerecently, a study on the use of a customised MiECC system was terminated prior to studycompletion due to venous air leakage. Others have also raised their concerns over patient safety by using aminiaturized ECC system, without a safety feature to remove venous air,5. The use of an air removal device at the venous side of the MiECCsystem could avoid air entering this system and may increase patient safety. A venousbubble trap (VBT) was designed as air removal device for air separation in the venousline of MiECC systems and it was also designed for air separation in the venous line ofminimized ECC circuits. The VBT was interconnected in the venous line of the MiECCsystem, and the air-removal was accomplished by a combination of two principles,centrifugal flow and bubble buoyancy. The 175-mm mesh screen separates air from bloodand enables removal of trapped air from both sides of the screen through the evacuationport. Many perfusionists add an accessory bubble trap in the intracavitary aspirator(vent) line before the main bubble trap and air evacuation port is connected to theautotransfusion system, allowing to block the air from the vent before the VBT. Othercircuit designs for MiECC have the vent line directly on the main VBT, the airevacuation port is connected to the autotransfusion system, or dynamic port connected tothe roller pump head. In the cardiopulmonary bypass consoles, there are automatedsystems for air purge control, detected through ultrasound sensors from the venous lineand bubble trap that activate the autoclamp and purge line.The use of minimally invasive extracorporeal circuits (MiECC) in cardiac surgery isexpanding. In this letter to the Editor, I emphasize the air evacuation management frombubble trap through various strategies. The prevention and management of macro and microgas embolism during minimally invasive extracorporeal circulation (ECC) is crucial. Inparticular, according to the classification of the Minimal Invasive ExtracorporealTechnologies International Society position paper, the types of MiECC II, III, and IVare equipped with bubble trap in the venous line. The improved biocompatibilityameliorates organ preservation and reduces transfusion of homologous bloodproducts


Introduction: Knee osteoarthritis (KOA) is characterized by articular cartilage degeneration. It has been widely accepted that the mechanical joint environment plays a significant role in the onset and progression of this disease. In silico models have been used to study the interplay between mechanical loading and cartilage degeneration, hereby relying mainly on two key mechanoregulatory factors indicative of collagen degradation and proteoglycans depletion. These factors are the strain in collagen fibril direction (SFD) and maximum shear strain (MSS) respectively.Methods: In this study, a multi-scale in silico modeling approach was used based on a synergy between musculoskeletal and finite element modeling to evaluate the SFD and MSS. These strains were evaluated during gait based on subject-specific gait analysis data collected at baseline (before a 2-year follow-up) for a healthy and progressive early-stage KOA subject with similar demographics.Results: The results show that both SFD and MSS factors allowed distinguishing between a healthy subject and a KOA subject, showing progression at 2 years follow-up, at the instance of peak contact force as well as during the stance phase of the gait cycle. At the peak of the stance phase, the SFD were found to be more elevated in the KOA patient with the median being 0.82% higher in the lateral and 0.4% higher in the medial compartment of the tibial cartilage compared to the healthy subject. Similarly, for the MSS, the median strains were found to be 3.6% higher in the lateral and 0.7% higher in the medial tibial compartment of the KOA patient compared to the healthy subject. Based on these intersubject SFD and MSS differences, we were additionally able to identify that the tibial compartment of the KOA subject at risk of progression.Conclusion/discussion: We confirmed the mechanoregulatory factors as potential biomarkers to discriminate patients at risk of disease progression. Future studies should evaluate the sensitivity of the mechanoregulatory factors calculated based on this multi-scale modeling workflow in larger patient and control cohorts. Osteoarthritis (OA) is the most common joint disease, with the knee being the most frequently affected joint. This complex multi-factorial disease is characterized by degenerative changes in articular cartilage, subchondral bone and by synovial inflammation . MechaniArticular cartilage, an avascular connective tissue, is composed of specialized chondrocyte cells embedded in an extracellular matrix (ECM), which consists mainly of water, proteoglycans (PGs) and a collagen fiber network. The interactions between these constituents dictate the mechanical behavior of cartilage and enable it to distribute mechanical load across the joint surface . Howeverin silico models have been developed. In particular, musculoskeletal (MSK) models have proven useful in estimating knee joint loading during locomotion, which has been found to be altered in patients with OA  subject displaying (fast) progression over a 2-year time frame. These subject-specific loading and boundary conditions were estimated based on experimental gait analysis data collected at baseline, prior to a 2-year follow-up, which is processed through a MSK modeling workflow. The proposed modeling pipeline in this study uses a unique MSK modeling-informed approach, where the subject-specific boundary and loading conditions are used to drive an FE model that is then used to evaluate the mechanical environment of cartilage and meniscus tissues within the knee joint. Firstly, mechanoregulatory factors known to underly cartilage constituent damage were evaluated, at baseline, to characterize the mechanical tissue environment prone to cartilage degeneration. More specifically, strain in fibril direction (SFD) and maximum shear strain (MSS) in the articular cartilage were evaluated as mechanoregulatory factors driving collagen degradation and PG depletion, respectively. Secondly, tissue responses in the menisci, a structure known to participate in strain mitigation and protection of the underlying cartilage tissue   modelingThe experimental gait analysis data is processed through the MSK OpenSim-JAM workflow. First, the generic model is scaled to the subject’s anthropometry, based on experimental marker data from the static trails. Then an inverse kinematics algorithm was used to estimate joint angles  based on a minimization of marker position between the model and experimental data . The conThe following specific outputs of the OpenSim-JAM were used as boundary conditions for the FE model: TF anterior-posterior translation, TF medial-lateral translation, TF internal-external rotation, knee flexion angle, varus-valgus moment and superior-inferior knee joint contact force. One representative trial for each subject was processed, more details on the outcome of the MS simulations are presented in FE models of the human knee joint were created using Abaqus software , that includes the tibial and femoral cartilage surfaces, (part of the) tibia bone and the menisci based on previous FE models developed by Identical generic knee joint geometries were used in the FE model and the MSK knee contact model to enforce geometrical consistency between the two workflows. Hexahedral meshes, generated in ANSA , were based on the meshes of the Cartilage was modeled as a fibril-reinforced poroviscoelastic (FRPVE) material including a biphasic (fluid and solid phases) description with a hyperelastic Neo-Hookean solid matrix representing the PGs and a viscoelastic fibril network representing collagen fibrils . The priThe time-dependent loading and boundary conditions derived from the MSK workflow were applied throughout the stance phase of the gait cycle. This was done by means of a transient analysis, more specifically a soils consolidation analysis, with an implicit FE scheme. The following subject-specific loading and boundary conditions derived from the MS model were implemented at the reference point of the femur in the FE model: Anterior-posterior translation, medial-lateral translation, internal-external rotation, knee flexion angle, varus-valgus moment and the superior-inferior TF joint contact force. This reference point was located between the medial and lateral femoral epicondyles and was tied to the femoral cartilage-bone interface. The origins of the ligaments were also tied to this reference point. The FE model was driven at this femoral reference point and thus the output of the MS model was extracted from the local coordinate system of the proximal tibia as this corresponds to the relative motion of the femur to the tibia.Femur bone was considered rigid and its effect was included in the FE model with encaster boundary condition on the femoral cartilage internal surface. The tibia bone was modeled as linear elastic for the purpose of facilitating the convergence of the model to a numerical solution. The bottom surface of the tibial bone was encastred. The following frictionless contact types were defined in the model as nodes to surfaces: Tibial cartilage to femoral cartilage, menisci to femoral cartilage, tibial cartilage to menisci and menisci to tibia bone. The assumption of frictionless contact is widely accepted as the standard in knee joint FE modeling, primarily because the main function of articular cartilage is to provide a smooth and frictionless surface for joint articulation and efficient load distribution across the joint surface .p,1, ɛp,2, ɛp,3 are the principal strains of the Green-Lagrangian strain tensor.F is the deformation gradient tensor and fe is the unit vector of the fibril orientation.This study analyzed maximum shear strain  outside the contact area between femoral and tibial cartilage and between menisci and tibial cartilage were considerably low and did not contribute to the analysis. The strains were extracted from the centroids of the tibial cartilage elements and element volumes were taken into account. Then, tibial cartilage tissue responses were evaluated at peak superior-inferior knee contact force, as tissue strains reached their absolute maxima at this time-point during the stance phase. Results were evaluated qualitatively based on strain responses at the tibial cartilage surface and quantitatively by means of violin plots of the tissue strains within the cartilage volume. This quantitative analysis was also restricted to the tibial cartilage volume related to the contact area.The maximum principal strain (MPS) of the logarithmic strain tensor was analyzed to reflect the overall tissue response of the menisci. The MPS was not directly associated with structural changes in the menisci. The tissue response was evaluated at peak superior-inferior knee contact force to be consistent with the evaluation of the tibial cartilage. Analogous to the evaluation of the tibial cartilage, a qualitative evaluation was done based on the strain at the (superior) surface of the menisci and a quantitative analysis was performed by means of violin plots of the tissue responses within the menisci. Here, the whole volume of the menisci was included in the quantitative analysis as (nearly) the whole surface of the menisci was in contact with either the femoral or tibial cartilage.During the majority of the stance phase, the MSS  and SFD For both lateral and medial compartments, the strain in fibril direction (SFD) was more elevated in the KOA compared to the control subject, with the median being 0.82% higher in the lateral and 0.4% higher in the medial compartment respectively . With thFor both compartments, the MSS of the KOA subject was more elevated compared to the control subject , with thThe maximum principal strain (MPS) is more elevated in the KOA subject compared to the control subject  The mediThis study is the first to compare key mechanoregulatory factors associated with cartilage tissue degeneration between a control subject and an early-stage KOA patient (KL 1) showing disease progression in 2 years. The study focused on two mechanoregulatory factors, namely, strain in the fibril direction (SFD) and maximum shear strain (MSS) and evaluation was performed using subject-specific loading conditions determined during the baseline stance phase of gait.in silico approach, the local cartilage strains in terms of SFD and MSS, were found to be higher for the KOA patient compared to the control subject throughout the majority of stance duration and at peak contact force. This shows how these intra-tissue strains during locomotion are distinct between the healthy and early KOA subject already at baseline despite the subjects’ similar demographics. During stance, this distinction is even more clear when evaluating the 75th percentile of the tissue strains that were elevated throughout the gait cycle in the OA subject. This is in line with previous suggestions that not only instantaneous loading that surpasses the threshold of cartilage degeneration, but also the accumulated load over time (cumulative load) during normal ambulatory activities, could induce cartilage degeneration  meniscectomy and meniscal subluxation have been associated with the degeneration process of cartilage . It is iThe altered joint level loading during gait in the patient with KOA impacts the local cartilage micro-environment such that constituent depletion occurs. Indeed, although the SFD was well below the threshold of degeneration (10%), MSS surpassed the threshold (30%) in 3.3% of the cartilage volume of the KOA subject. This would suggest a potential risk of PG depletion to drive the OA progression rather than collagen degeneration, which is highly relevant as it has been suggested that damaged cartilage can suffer from PG depletion under physiological loading conditions  and thatFinally, in this study, personalized loading conditions were estimated from MSK modeling and used to drive the FE model to study the tissue strain responses. These personalized loading conditions estimated during gait differed between the control subject and the KOA patient, with higher inferior-superior contact force and knee adduction moment, as well as higher knee flexion in the KOA compared to the control subject. Previous studies have shown that the aforementioned characteristics are distinctive for KOA subjects . AdditioIn this study, proof of concept data was obtained from two participants which could serve as a stepping stone for future analysis where more participants are included. It would be particularly interesting to include non-progressive KOA subjects as this would provide more information and likely more insight into the relation between localized tissue strains and cartilage degeneration. It must be noted that executing the FE workflow is a time-consuming task with high computational costs, and it can be challenging to achieve convergence of the model. The advantage of the implemented modeling approach is that it uses generic geometries consistent with the MSK pipeline. This alleviates the need for re-meshing of the geometries, which saves a significant amount of time, however at the expense of losing personalized details on the articular cartilage geometry. Thus, variations in cartilage thickness are not accounted for. Although the use of a generic mesh was deemed acceptable in this study, as no cartilage thinning was assumed to be present in the KOA patient with KL score 1, personalized geometry, in particular thickness, can further enhance the accuracy of strain predictions within the cartilages and menisci.Although subject-specific loading conditions were applied, further personalization of the model in terms of cartilage thickness and geometry, knee contact with friction or tissue material properties in the FRPVE material model based on the disease state of the subject  needs to be considered and might affect the SFD and MSS measures. Although state-of-the-art, the use of similar material parameters for a healthy and KOA subject is a limitation as it can alter the tissue mechanics significantly. In future work, experimental non-invasive characterization of subject-specific material parameters  may allow more fine-tuning of the estimation of mechanical parameters driving the mechanoregulatory algorithm. However, in this study, given the consistent implementation of the entire modeling workflow in both subjects and the inclusion of subjects with similar demographics, we are confident in the comparability of the FE model results and the validity of the conclusions regarding the relative differences between the control and KOA subjects. Furthermore, Altered cartilage tissue response, namely, local strain concentrations, seem to be present at the origin of the collagen split lines where there is a discontinuity in the fibrils. This could be an underlying cause of volume surpassing the MSS threshold in the control subject, suggesting PG depletion. These local strain concentrations can be considered and compensated for in adaptive modeling workflows. Studies by in vivo conditions is not clear, given that the current thresholds were selected based on outcomes from in vitro experiments , on the resulting tissue strains.in silico modeling approach to analyze key mechanoregulatory factors for cartilage degeneration. These mechanoregulatory factors were able to distinguish between a healthy and progressive early-stage KOA subject and even more, able to identify the tibial compartment at risk of progression. Furthermore, evaluated tissue responses in the menisci can be related to specific OA loading conditions. Therefore, the mechanoregulatory factors analyzed could potentially serve as functional biomarkers allowing discrimination of patients at risk of (fast) disease progression. As such, this study presents a first step towards in silico-informed screening in the context of musculoskeletal disorders. Following further validation in larger cohorts, this could not only aid in earlier diagnosis, personalized treatment provision and prediction of progression as well as monitoring for patients with KOA, but may also provide novel fundamental insights into the intricate interplay between mechanical tissue loading during locomotion, the local cartilage micro-environment in vivo and consequent cartilage tissue degeneration.Patient-specific gait data at baseline were processed through a multi-scale


Editorial on the Research TopicOpen issues in the diagnosis and management of tricuspid regurgitationTricuspid valve regurgitation (TR) is a highly prevalent valvular heart disease with a prevalence of moderate or severe TR ranging from 7.1% in the Framingham Heart Study .Previously considered “the forgotten valve” perhaps because of lack of tailored treatment options as well as lack of data around its importance as a prognostic factor in cardiovascular disease, several data have shown that severe TR is an independent prognostic factor . This paConservative management of tricuspid regurgitation (TR) proved ineffective in reducing symptoms and progression of the right heart failure picture with worsening cardiac, renal, and liver functions. Recently, several percutaneous options have been trialed showing promising preliminary results in terms of improvement of symptoms and quality of life and reduction of hospitalization , 5.The aim of this special issue  is to giGavazzoni et al. highlighted the prognostic importance of the pathogenetic remodeling underlying TR, showing that atrial secondary TR is associated to more favorable outcome than the ventricular phenotype. Atrial secondary TR has shown less valvular remodeling and better RV longitudinal function, as evaluated with state-of-the-art methods. Both type of secondary TR and right ventricular function have an impact on mortality or event-free survival.The special issue will kick off with a discussion around the problem of quantification of TR and the evaluation of pathophysiological mechanisms. For instance, apart from the primary TR mechanisms , the more prevalent functional TR disease has been recently dissected into two different pathophysiological mechanisms: one due to annular remodeling  vs. one due to apical tethering forces (ventricular TR) . On thisMuraru et al. identified the reference values for tricuspid annulus geometry and dynamics using a commercially available three-dimensional echocardiography software package dedicated to the tricuspid valve, thus overcoming the intrinsic limitations of 2-dimensional linear measurements and giving sex-specific and indexed to BSA cut offs. Based on the wide scientific experience of their group on tricuspid valve and right heart chambers, this is a seminal work paving the way to subsequent possible prognostic relevance of 3-dimensional geometry of tricuspid annulus.Further, Baratto et al. The evaluation of cardio-pulmonary adaptation at rest and during exercise is an important aspect to be evaluated in patients with symptoms of heart failure. In particular severe functional TR complicating HFpEF led to pulmonary vascular de-recruitment and relative left heart underfilling, with important implications for HFpEF pathophysiology.TR has an important additional impact of the hemodynamics of patient with heart failure with preserved ejection fraction (HFpEF), as highlighted by Alperi et al. summed up the transcatheter systems used for TR correction under clinical use or clinical evaluation with their technical features with updated description of the current evidence in this challenging and evolving field.In the interventional part of this issue, Sannino et al. detailed the peculiar clinical and echocardiographic outcomes of transcatheter tricuspid valve interventions: in particular transcatheter options significantly reduces TR severity and increases forward stroke volume and is associated with improved survival at 1 year compared with patients without procedural success. It is important to underline that long-term outcomes compared with medical therapy await the results of ongoing pivotal trials, as the recent TRILUMINATE trial (TE trial .Haurand et al. studied if the use of deep sedation, as nowadays routinely used in transcatheter aortic valve implantation, impact on the procedural results of transcatheter TV repair: procedures performed under deep sedation, as opposed to the standard that is general anesthesia, were as effective and safe with similar low complication rates, showing the possible feasibility of less invasive anesthesiologic assistance during such procedures.This special issue highlights the evolving field of TR interventions and the importance of diagnosis of degree of TR as well as the mechanisms underpinning such disease. The focus of such endeavor is relevant as it serves the higher aim of ameliorating the prognosis and symptoms of this large population of patients suffering from this no-more-forgotten condition.


This clinical report details the successful rehabilitation of a 63-year-old male patient with severe tooth wear, a reduced vertical dimension of occlusion, and esthetic concerns. The Hobo twin-stage procedure addressed these issues while improving the patient's oral health and quality of life. After ensuring adequate oral hygiene, the treatment began with scaling and root planning, followed by diagnostic impressions. An occlusal splint was fabricated, followed by a diagnostic wax-up and tooth preparation. Full-arch impressions of prepared teeth were made using the addition of silicon elastomeric impression material, and chairside provisional crowns were fabricated. The working casts were mounted on a semi-adjustable articulator, and the metal copings were tried on before being built up in porcelain. The patient achieved successful outcomes and expressed satisfaction with the treatment. The Hobo twin-stage technique and porcelain-fused-to-metal crowns can be viable approaches for restoring the teeth's form and function while enhancing the patient's oral health and esthetics. However, regular follow-up appointments and good oral hygiene maintenance are essential for the long-term success of the treatment. The loss of natural tooth structure due to generalized attrition is a significant challenge in restorative dentistry . AlthougThis clinical report highlights the use of the Hobo twin-stage procedure to rehabilitate a patient suffering from generalized attrition and reduced vertical dimension of occlusion (VDO). The Hobo twin-stage technique creates anterior guidance to achieve a pre-planned and harmonious posterior disocclusion in line with the condylar path ,4. The tA 63-year-old male presented to the Department of Prosthodontics with a chief complaint of worn-out teeth and difficulty chewing. He had no significant medical history and reported no known allergies or adverse drug reactions. He was cooperative and willing to undergo treatment. Clinical examination revealed severe generalized attrition of all teeth and a decreased VDO Figures -2. The pThe treatment plan for the patient with severe tooth wear and reduced VDO included full mouth restorations using either the Hobo twin-stage or Pankey-Mann Schuyler technique. Ultimately, the decision was made to use the Hobo twin-stage procedure for full mouth rehabilitation with PFM crowns. This was chosen due to the advantages of single-step tooth preparation, pre-set values, and the absence of the need for condylar and lateral records.Clinical procedureThe procedure began with scaling and root planing to promote dental hygiene and periodontal health. Gingivectomy was performed to establish the gingival zenith distal to the long axis of the maxillary central and lateral incisors and along the long axis of the maxillary canines. Diagnostic impressions were made after ensuring optimal dental hygiene and complete healing of the tissues. A facebow record was made and transferred to the semi-adjustable articulator . The next step involved making a centric record and using it to mount the mandibular cast onto the articulator Figure .Afterward, the patient's adaptability to the new VDO was observed for six weeks using an occlusal splint at a 2 mm increase in VDO. A diagnostic wax-up and a putty index followed this. The teeth were then prepared according to the standard protocol for PFM restoration with minimal occlusal reduction 0.3-0.5 mm), and a complete arch impression was made with elastomeric impression material  Figures -5. Using mm, and A facebow record was made and the working casts were mounted on a semi-adjustable articulator with the facebow Figure .To transfer the VDO and CR, the temporary provisional crowns from the left posterior section were removed. In contrast, the temporary provisional crowns from the right and anterior sections were left intact. A piece of record material  was placed between the prepared teeth on the left posterior section. The same procedure was repeated in the left and anterior sections, and the mandibular cast was mounted using three segmental interocclusal records Figure .Finally, non-eugenol temporary cement  was used to cement the temporary provisional crowns Figure .After creating wax patterns and casting them, metal copings were tried in the patient's mouth to ensure a proper fit Figure . SubsequIn the second phase, the anterior section was reattached to the cast, and the condylar and incisal guidance was set to Hobo's condition 2 to achieve posterior disocclusion Table .Porcelain build-up for the anterior teeth was then carried out to ensure that the maxillary and mandibular incisors were contacted during protrusive movement and that the maxillary and mandibular canines on the working side came into contact during lateral movement. As a result, the anterior guidance was established, and the standard amount of disocclusion was produced Figure .Finally, the PFM crowns were cemented in place using polycarboxylate cement Figure -14. The Generalized attrition is a common problem among older adults, leading to functional, esthetic, and occlusal concerns . The resThe fundamental principles of the Hobo twin-stage technique require the establishment of adjustment values for an articulator to replicate a standard cusp angle and a standard amount of disocclusion. To achieve conditions 1 and 2, specific calculations are used to select the necessary adjustment values for the articulator. The standard value for the sagittal protrusive effective cusp angle is 25 degrees; thus, it is recommended to adjust both the condylar path and anterior guide table to 25 degrees and fabricate cusps without anterior teeth to achieve a balanced articulation. This enables uniform fabrication of the 25-degree cusp angle, which is the adjustment value required for the articulator to attain condition 1. Once the cusps have been waxed to the standard angle value, the anterior guidance should be established to replicate a standard amount of disocclusion. To generate the standard amount of disocclusion on molars and fabricate physiological anterior guidance, a combination of 40 degrees for the condylar path and 45 degrees for the anterior guide table is used. This is the adjustment value for the articulator required to achieve condition 2 ,7.In 1984, Turner and Missirlian proposed a classification system for the treatment of severely worn dentition based on the degree of loss of VDO and the amount of available space for restoration ,11.Using provisional restorations allowed for evaluating the restored VDO before the final restorations were fabricated. This ensured that any discrepancies or discomfort in the new occlusal relationship could be addressed before the final restorations were cemented. The use of provisional restorations also allowed for the development of proper occlusal contacts and tooth contours, which were transferred to the final restorations ,13.Various occlusal schemes have been proposed for full mouth rehabilitation, such as PMS, Hobo's twin table, the Hobo twin-stage technique, Youdelis, and Nyman and Lindhe Scheme ,14. AmonPFM crowns, in this case, allowed for the restoration of the lost tooth structure while improving the esthetic appearance of the teeth . Using pThis case report illustrated the successful application of the Hobo twin-stage technique for full-mouth rehabilitation using PFM crowns to address a patient's severe tooth wear and reduced VDO. The treatment provided a viable option for restoring the form and function of the teeth while improving the patient's oral health and esthetics. The careful planning, accurate preparation, and meticulous execution of the treatment resulted in a successful outcome, instilling confidence and satisfaction in the patient. The Hobo twin-stage procedure can significantly improve the outcomes of restorative dentistry and provide long-lasting benefits to patients with complex dental problems. However, each patient's case is unique, and careful planning and a comprehensive approach should be taken to determine the optimal treatment plan.


Multidrug-resistant bacteria are an emerging issue which is not restricted to clinics and the health care sector, but is increasingly affecting the environment. Multidrug-resistant bacteria are released into the environment via wastewater, improperly inactivated or disposed of waste and by applying organic fertilizers to agricultural fields, etc. The released bacteria are able to survive or even thrive in the environment and transfer their antibiotic resistance genes (ARG) to the autochthonous microbiome in aquatic environments, soils or even to plants/crops consumed by humans. In some instances, they die, releasing their DNA, which is then taken up by other bacteria in the environment. The latter mechanism is denominated transformation. The bacteria which can take up foreign “naked” DNA from the environment are naturally competent. In the first case, in which the released bacteria can survive in the environment, the major mechanism driving the dissemination of ARGs is conjugative transfer. The key players of this mechanism are conjugative plasmids, mobilizable plasmids, and very likely also integrative conjugative elements (ICEs) and genomic or pathogenicity islands ,2,3. TheEscherichia coli host factors on the transfer frequency of the broad-host-range plasmid pKJK10. They confirmed the role of the genes fliF, fliK, kefB and ucpA in the donor ability of conjugative elements by validating defects in the conjugation efficiency of the corresponding E. coli strain single-gene deletion mutants. Based on the cellular functions of these genes, the authors suggested that motility and energy supply, as well as the intracellular pH or salinity of the donor strain strongly affect the efficiency of plasmid transfer. Thus, the work of Van Wonterghem and coworkers could facilitate the search for targets for the development of conjugation inhibitors, which could be administered together with antibiotics to treat bacterial infections more effectively [In this Special Issue, eight articles, five research articles, one research communication, and two review articles addressed the main issues relating to the topic of the Special Issue. The paper of Korotetskiy and coworkers analyzed whole-genome sequences of pathogenic Gram-positive and Gram-negative isolates from the same hospital environment to elucidate evolutionary trends associated with horizontal gene transfer, mutations and DNA methylation patterns. They concluded that genotyping through third-generation sequencing and determination of patterns of genome methylation can be instrumental for monitoring the distribution of clonal lines of pathogens due to methylation patterns associated with specific pathogens . Van Wonectively .Bacillaceae were the most abundant family present in the commercial chili powders. Antibiotic resistance profiles of nosocomial pathogens detected in the chili samples revealed the presence of extended spectrum beta lactamases (ESBLs) and Metallo-beta-lactamases. These findings may facilitate developing procedures for microbial monitoring during chili powder production [Hernández Gómez et al. studied the microbial community of commercial Mexican chili powder and its resistome. oduction .intI1 and korB, from the start to the end of composting. Thus, thermophilic composting can decrease the horizontal spread of ARGs and could be a suitable treatment for the recycling of human excreta [Colgan et al. and Werner et al. investigated the effect of different types of manure and compost generated by thermophilic composting of human excreta amended by green cuttings and sawdust on the composition of the bacterial community, abundance of bacterial pathogens and ARGs, respectively. The first study showed that the type of ARGs which persisted in soils was strongly dependent on the origin of the manure (cattle manure versus swine manure). They concluded that the distinct temporal dynamics of the resistance gene distributions in soil for each manure type could be used to develop potential mitigation strategies . Werner  excreta .Miguel-Arribas and coworkers studied the presence of antitermination systems in conjugation operons of different conjugative plasmids of Gram-positive origin. These antitermination systems allow differential regulation of subsets of conjugation genes. Thus, they are involved in fine tuning of the expression of distinct components of the conjugation systems. Interestingly, the Inc18 family of Gram-positive broad-host-range conjugative plasmids does not contain an antitermination system. The possible advantages of the lack of an antitermination system in context of a broader conjugative host range of plasmids lacking such a system have been discussed .Rozman and coworkers performed a systematic literature review on the reduced susceptibility and increased resistance of bacteria against disinfectants. They showed that reduced susceptibility to disinfectants and problems potentially related to antibiotic resistance in clinically relevant bacterial strains are increasing. The authors recommended the rotation of disinfectants, where one disinfectant should be replaced by another that has a different mechanism of action. In addition, they pointed out the necessity of developing and adopting strategies to control disinfectant resistance development . In theiIn summary, there is an urgent need for an in-depth understanding of the diverse horizontal transfer mechanisms and their contribution to the spread of ARGs to develop efficient mitigation strategies. Moreover, innovative strategies must soon be developed to minimize the release of antibiotic resistant bacteria into the environment to avoid risking the efficient antibiotic treatment of bacterial infections.