Search

BACKGROUND: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcription factor nuclear factor-κB (NF-κB) is activated by the various stimulation such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NF-κB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NF-κB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. MATERIALS AND METHODS: Safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSChs) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover were carried out. The efficacious concentration of Decoy determined from the rNSChs was then applied to human nasal septal cartilage (hNSC) in vitro and analyzed for PG turnover, the levels of inflammatory markers, and catabolic enzymes in explant-conditioned culture medium. RESULTS: Over the range of Decoy conditions and concentrations, no inhibition of PG synthesis or cytotoxicity was observed. Decoy at 10 μM effectively inhibited PG degradation in the hNSC explant, prolonging PG half-life by 63% and decreasing matrix metalloprotease 3 (MMP-3) by 70.7% (p = 0.027). CONCLUSIONS: Decoy may be considered a novel chondroprotective therapeutic agent in cartilage transplantation due to its ability to inhibit cartilage degradation due to inflammation cytokines.

ABSTRACT Background/Aims Methods Results Conclusions Transient apical breakdown (TAB) is a phenomenon that indicates temporary apical periodontal destruction and root resorption after tooth luxation injuries, followed by the healing process of the dental pulp. Andreasen in 1986, reported that TAB was seen in approximately 4.2% of all luxation injuries. However, there have been no reports thereafter on the types and frequency of the luxation traumatic injuries in which TAB occurs. Therefore, this retrospective study was aimed to assess the incidence and pathogenesis of dental trauma‐induced TAB and to suggest a possible mechanism of subsequent healing based on a series of cases.Data analysis included mature teeth (n = 56) of 49 patients aged 9–30 years who presented in a private dental office over a period of 10 years (2012–2022) to investigate the incidence and healing sequala of TAB.TAB was observed in 43.8% of subluxation, 62.5% of extrusive luxation, and 75% of lateral luxation injuries. The average age of patients who developed TAB was 14.5 years, ranging from 9 to 28 years old.TAB can be expected in many cases of luxation injuries with minimal dislocation. Therefore, mild injuries (subluxation, extrusion, and lateral luxation), may exhibit spontaneous healing, recovery of dark discoloration of the crown, disappearance of a periapical radiolucent lesion and return to normal response to EPT as long as 12 months after the traumatic injury. Thus, a decision to perform endodontic treatment in these cases might be postponed until clear evidence for an infection exists. [ABSTRACT FROM AUTHOR]

Introduction: The bio-stimulatory effects of low-intensity ultrasound on dental tissues which were clinically introduced in 2004 demonstrated a reduction in root resorption in maxillary premolars subjected to a force level of 50 g. Similar results by applying a torque of 50 g to the maxillary premolars were obtained in 2016; however, the effects of low-intensity pulsed ultrasound (LIPUS) on the presence of high-intensity forces are not yet known. Aim: The purpose of this study was to examine the effects of LIPUS on a sample of 40 patients. Methods: The analysis was conducted by applying two forces to teeth no. 14 and 24, each with an intensity greater than 50 g, and applied at two different points on the coronal surface. Subsequently, LIPUS was applied daily for 20 minutes to tooth no. 14, while tooth no. 24 served as a control. The study lasted for 28 days. Results: Overall, the group treated with LIPUS demonstrated an improvement in the average total volume and percentage of root resorption compared to the control group. The same results emerged for the diameter, depth, and surface of the gaps of resorption. Conclusion: This study showed that it was possible to reduce root resorption in the presence of forces with intensities greater than 50 g. Nevertheless, a longer period of study will make it possible to obtain more rational results as to the effectiveness of low-intensity ultrasound on root resorption induced by orthodontic treatment. [ABSTRACT FROM AUTHOR]

The thermal state of a magma reservoir controls its physical and rheological properties: at storage temperatures close to the liquidus, magmas are dominated by melt and therefore mobile, while at lower temperatures, magmas are stored as a rheologically locked crystal network with interstitial melt (crystal mush). Throughout the lifetime of a magmatic system, temperature fluctuations drive transitions between mush-dominated and melt-dominated conditions. For example, magma underplating or magma recharge into a crystal mush supplies heat, leading to mush disaggregation and an increase in melt fraction via crystal resorption, before subsequent cooling reinstates a crystal mush via crystal accumulation and recrystallisation. Here, we examine the textural effects of such temperature-driven mush reprocessing cycles on the crystal cargo. We conducted high-P-T resorption experiments during which we nucleated, grew, resorbed, and recrystallised plagioclase crystals in a rhyolitic melt, imposing temperature fluctuations typical for plumbing systems in intermediate arc volcanoes (20–40 °C). The experiments reproduce common resorption textures and show that plagioclase dissolution irreversibly reduces 3D crystal aspect ratios, leading to more equant shapes. Comparison of our experimental results with morphologies of resorbed and unresorbed plagioclase crystals from Mount St. Helens (MSH) (USA) reveals a consistent trend in natural rocks: unresorbed plagioclase crystals (found in MSH dacite, basalt and quenched magmatic inclusions [QMIs]) have tabular shapes, while plagioclase crystals with one or more resorption horizons (found in MSH dacite, QMIs, and mush inclusions) show more equant shapes. Plagioclase crystals showing pervasive resorption (found in the dacite and mush inclusions) have even lower aspect ratios. We therefore suggest that crystal mush maturation results in progressively more equant crystal shapes: the shapes of plagioclase crystals in a magma reservoir will become less tabular every time they are remobilised and resorbed. This has implications for magma rheology and, ultimately, eruptibility, as crystal shape controls the maximum packing fraction and permeability of a crystal mush. We hypothesise that a mature mush with more equant crystals due to multiple resorption–recrystallisation events will be more readily remobilised than an immature mush comprising unresorbed, tabular crystals. This implies that volcanic behaviour and pre-eruptive magmatic timescales may vary systematically during thermal maturation of a crustal magmatic system, with large eruptions due to rapid wholesale remobilisation of mushy reservoirs being more likely in thermally mature systems. [ABSTRACT FROM AUTHOR]

The physicochemical properties of grafting materials affect the quality of the osteointegration, resorption rate, and the new bone (NB) formation. This study assessed the physicochemical properties and integration of a low temperature deproteinized bovine bone xenograft (BBX), referred to as optimized MoaBone® (OMB). This novel BBX was physiochemically characterized both pre and post chemical bleaching and sterilization by gamma irradiation. OMB was compared to two commercial BBX; Bio‐Oss® (BO) and MoaBone® (MB) using a rabbit cranial model. Residual graft and NB were quantified using histology and micro‐computed tomography. Results showed that chemical treatment and gamma irradiation had limited effect on the surface texture. A significant decrease in the collagen content was detected post chemical treatment and in the carbonate content post gamma irradiation. There was no evidence of inflammatory infiltrate, necrosis, or connective tissue encapsulation, and a significant increase of NB in all grafted sites as compared to untreated defects could be observed. However, there was no statistically significant difference between the grafted sites. We conclude that chemical treatment and terminal sterilization strongly impact the final graft's properties. OMB graft showed equivalence with BO for in vivo bone formation and potentially results in lower levels of graft retention. [ABSTRACT FROM AUTHOR]

To investigate the role of the paravertebral lymphatic system in the nucleus pulposus herniation (NPH) resorption and the inflammation regression. Clinical specimens (n = 10) from patients with lumbar disc herniation (LDH) were collected, C57BL/6 (n = 84) and conditional Vegfr3 knockout mice (n = 14) were used. Immunofluorescence staining detected lymphatic vessels (LVs) and NP cells. Near-infrared imaging assessed lymphatic drainage function, and Alcian Blue/Orange determined inflammation. Lymphangiogenesis was observed in the herniated NP of patients with LDH, and the proportion of capillary LVs was higher than that of collecting LVs (mean 68.2% [95% confidence interval: 59.4, 77.1]). In NPH mice, NP cells were detected in paravertebral tissue (38.6 [32.0, 45.2]) and draining lymph nodes (dLN) at 4 h (76.9 [54.9, 98.8]). A significant increase of NP cells in dLNs was observed at 24 h (157.1 [113.7, 200.6]). Most of the herniated NP cells were cleared in paravertebral tissue after 1 week (7.5 [4.4, 10.6]), but disc inflammation peaked at 1 week (19.9% [14.7, 25.1]), along with persistent lymphangiogenesis (9.5 [7.2, 11.8]). However, conditional Vegfr3 knockout mice exhibited impaired lymphangiogenesis (5.7 [4.4, 7.0]) and herniated NP cell clearance (6.1 [1.8, 10.5]) during NPH, leading to exacerbated disc inflammation (23.7% [19.3, 28.2]). The paravertebral lymphatic system is involved in the NPH resorption and inflammation regression. Promoting lymphangiogenesis may be a novel strategy for facilitating NPH resorption and inflammation regression in patients with LDH. [ABSTRACT FROM AUTHOR]

Background: The Latarjet procedure was developed for the treatment of anterior shoulder instability in young, high-demand patients with attritional glenoid bone loss, whose risk of redislocation following primary dislocation may exceed 90%. Coracoid graft osteolysis and prominent screws are commonly observed in late computed tomography (CT) scans of patients who re-present following the procedure, but the clinical relevance of osteolysis in the overall Latarjet cohort is undetermined. We aimed to evaluate clinical and radiological outcomes in patients who underwent the Latarjet procedure, and to determine if severe coracoid graft osteolysis compromised clinical outcomes. Methods: This was a retrospective analysis of patients who underwent the open Latarjet procedure. Patients were invited via an e-questionnaire that contained a Western Ontario Shoulder Instability Index (WOSI), and queried about redislocation and reoperation since index surgery. Preoperative glenoid bone loss was calculated on CT using the best-fit circle method. Osteolysis was graded (0, screw head buried in graft; 1, screw head exposed; 2, threads exposed; 3, complete resorption/severe osteolysis) at the level of the proximal and distal screws respectively, on axial CT scans performed ≥ 12 months postoperatively. Results: Between 2011 and 2022, a single surgeon performed 442 Latarjet procedures. One hundred fifty eight patients responded to the questionnaire at median (interquartile range [IQR]) 44 (27-70) months postoperatively, among whom the median (IQR) WOSI score was 352 (142-666) points (0 = best, 2100 = worst). Recurrent anterior instability occurred in 3/158 (2%) patients. One patient required reoperation for this indication. Among patients who had CT scans ≥ 12 months postoperatively (median [IQR] 40 [29-69] months), 1 patient developed severe osteolysis around both screws (WOSI = 90), 17/62 (27%) patients developed severe osteolysis around 1 screw, all of which were proximal (median [IQR] WOSI = 235 [135-644]), and 44/62 (71%) patients did not develop severe osteolysis around either screw (median [IQR] WOSI = 487 [177-815]). There were no statistically significant differences in WOSI scores between groups based on the presence of severe osteolysis. Conclusion: The Latarjet is reliable procedure that has a low rate of redislocation and reoperation. Severe coracoid graft osteolysis occurs with time, and always affects the proximal graft first. The presence of severe osteolysis did not compromise clinical outcomes.

Pregnancy involving intricate tissue transformations governed by the progesterone hormone (P4). P4 signaling via P4 receptors (PRs) is vital for endometrial receptivity, decidualization, myometrial quiescence, and labor initiation. This study explored the role of TCF23 as a downstream target of PR during pregnancy. TCF23 was found to be expressed in female reproductive organs, predominantly in uterine stromal and smooth muscle cells. Tcf23 expression was high during midgestation and was specifically regulated by P4, but not estrogen. The Tcf23 knockout (KO) mouse was generated and analyzed. Female KO mice aged 4-6 months exhibited subfertility, reduced litter size, and defective parturition. Uterine histology revealed disrupted myometrial structure, altered collagen organization, and disarrayed smooth muscle sheets at the conceptus sites of KO mice. RNA-Seq analysis of KO myometrium revealed dysregulation of genes associated with cell adhesion and extracellular matrix organization. TCF23 potentially modulates TCF12 activity to mediate cell-cell adhesion and matrix modulation in smooth muscle cells. Overall, TCF23 deficiency leads to impaired myometrial remodeling, causing parturition delay and fetal demise. This study sheds light on the critical role of TCF23 as a dowstream mediator of PR in uterine remodeling, reflecting the importance of cell-cell communication and matrix dynamics in myometrial activation and parturition. [ABSTRACT FROM AUTHOR]

Root resorption is a naturally occurring phenomenon in primary dentition for the exfoliation of teeth. Root resorption in permanent teeth is a pathologic process that is not only specific to trauma or infections of pulp but also likely to occur due to untoward sequelae of any orthodontic procedures. There are internal and external types of root resorption, each having its variety. External apical root resorption is primarily asymptomatic, thereby mostly accidentally revealed by radiographic examination. Early diagnosis is essential to prevent, and manage the consequences, and to provide an optimal treatment option for the patient. [ABSTRACT FROM AUTHOR]

Study Design. Prospective, case series. Objective. To identify and characterize any differences in specific patient factors, MRI findings, features of spontaneous disc resorption, and outcomes between patients with single-level and multilevel LDH. Background. Lumbar disc herniation (LDH) is one of the most common spinal pathologies worldwide. Though many cases of LDH resolve by spontaneous resorption, the mechanism underlying this "self-healing" phenomenon remains poorly understood, particularly in the context of multilevel herniations. Methods. A one-year prospective study was conducted of patients presenting with acute symptomatic LDH between 2017 and 2019. Baseline demographics, herniation characteristics, and MRI phenotypes were recorded before treatment, which consisted of gabapentin, acupuncture, and the avoidance of inflammatorymodulating medications. MRIs were performed approximately every three months after the initial evaluation to determine any differences between patients with single-level and multilevel LDH. Results. Ninety patients were included, 17 demonstrated multilevel LDH. Body mass index was higher among patients with multilevel LDH (P<0.001). Patients with multilevel LDH were more likely to exhibit L3/L4 inferior endplate defects (P=0.001), L4/L5 superior endplate defects (P=0.012), and L4/L5 inferior endplate defects (P= 0.020) on MRI. No other differences in MRI phenotypes (e.g. Modic changes, osteophytes, etc.) existed between groups. Resorption rate and time to resolution did not differ between those with single-level and multilevel LDH. Conclusions. Resorption rates were similar between single-level and multilevel LDH at various time points throughout one prospective assessment, providing insights that disc healing may have unique programmed signatures. Compared with those with singlelevel LDH, patients with multilevel herniations were more likely to have a higher BMI, lesser initial axial and sagittal disc measurements, and endplate defects at specific lumbar levels. In addition, our findings support the use of conservative management in patients with LDH, regardless of the number of levels affected. [ABSTRACT FROM AUTHOR]

Bioresorbable stents represent a revolutionary treatment for coronary artery disease. Such a device offers the prospect for complete naturalization of artery lumen after strut resorption and restoration of vasomotion while curtailing the duration of dual anti‐platelet therapy. The prototype bioresorbable scaffold (BRS—ABSORB GT1) demonstrated good feasibility and safety in the initial studies compared to metallic drug eluting stent but later fell out of favor due to multiple report of stent thrombosis and target lesion failure. Unpredictable resorption of struts turned out to be one of the "Achilles heel" of the BRS and stent strut were still visible in vessel on optical coherence tomography (OCT) at 3 years. We report a case of differential resorption of two ABSORB BRS implanted simultaneously in the same patient by the same operator. Follow up coronary angiogram revealed only minimal plaques on right coronary artery (RCA) and left anterior descending artery (LAD). The BRS were identified on cine‐angiogram by their radio‐opaque markers at both ends. The OCT run in LAD artery revealed "ghost remnants" of BRS struts in LAD, whereas the RCA BRS had completely healed with minimal "ghost" struts. The ghost remnants of BRS resembled the original "Check box" appearance on OCT during the index implantation. [ABSTRACT FROM AUTHOR]

Global climate change is expected to have a significant impact on ecosystems worldwide, especially for alpine meadows which are considered as one of the most vulnerable components. However, the effects of global warming on the plant nitrogen–phosphorus stoichiometry and resorption in alpine meadows remain unclear. Therefore, to investigate the plant nitrogen–phosphorus stoichiometry and resorption in alpine meadows on the Qinghai-Tibet Plateau, we conducted an artificial warming study using open-top chambers (OTCs) over the 3 years of warming period. We selected three dominant species, four height types of OTCs (0.4, 0.6, 0.8 and 1 m) and four warming methods (year-round warming, winter warming, summer–autumn–winter warming and spring–summer–autumn warming in the experiment) in this experiment. In our study, soil temperature significantly increased with increasing the height of OCTs under the different warming methods. Kobresia pygmaea presented an increase in nitrogen (N) limitation and Kobresia humilis presented an increase in phosphorus (P) limitation with increasing temperature, while Potentilla saundersiana was insensitive to temperature changes in terms of nitrogen and phosphorus limitations. Both nitrogen resorption efficiency:phosphorus resorption efficiency and N:P trends in response to rising temperatures were in the same direction. The differential responses of the chemical stoichiometry of the three species to warming were observed, reflecting that the responses of nitrogen and phosphorus limitations to warming are multifaceted, and the grassland ecosystems may exhibit a certain degree of self-regulatory capability. Our results show that using chemical dosage indicators of a single dominant species to represent the nitrogen and phosphorus limitations of the entire ecosystem is inaccurate, and using N:P to reflect the nutritional limitations might have been somewhat misjudged in the context of global warming. [ABSTRACT FROM AUTHOR]

Objectives: Many treatment options accepted for unsalvageable traumatized teeth in adults would seem contraindicated in children and adolescents. Instead, growing patients need interim restorative measures, thus extensively preserving their local bone and soft tissue structures and, ideally, preparing the involved site for later definitive restoration while they transform to skeletal maturity. This narrative topic review addresses the interim management in case of very deep intra-extra-alveolar fractures, extensive infection-related root resorption, tooth ankylosis, and anterior tooth loss in growing patients, and seeks to empower the clinician to select the appropriate treatment approach. Data sources: The literature up to 2021 was reviewed based on several scoping searches on PubMed and the Cochrane Library using relevant terms. Due to the complexity of the topic (with various poor prognosis scenarios and the differing therapeutic options), a systematic review was deemed inappropriate. Conclusion: Suitable interim treatment options include extrusion of teeth showing deep intra-extra-alveolar fractures, and decoronation of ankylosed teeth as well as resin-bonded fixed dental prostheses, natural tooth pontics, and primary tooth autotransplantations after tooth loss. The interim management options described in this article represent compromises chosen in the absence of better alternatives after a careful risk-benefit analysis. However, if adequately performed, the presented treatment options have the potential to achieve the temporary restoration of function and esthetics in growing patients. Close clinical and (if appropriate) radiologic monitoring of these patients is considered mandatory to ensure early detection of possible complications that might jeopardize or could render impossible subsequent therapeutic measures. [ABSTRACT FROM AUTHOR]

• Heparan sulfate oligosaccharides selectively inhibit the collagenase activity of cathepsin K. • The inhibition mechanism involves heparan sulfate-induced dimerization of cathepsin K. • Heparan sulfate stabilizes the active conformation of cathepsin K and extents its half-life. • Structurally defined heparan sulfate oligosaccharides inhibit bone resorption without affecting osteoclasts differentiation. Cathepsin K (CtsK) is a cysteine protease with potent collagenase activity. CtsK is highly expressed by bone-resorbing osteoclasts and plays an essential role in resorption of bone matrix. Although CtsK is known to bind heparan sulfate (HS), the structural details of the interaction, and how HS regulates the biological functions of CtsK, remains largely unknown. In this report, we discovered that HS is a multifaceted regulator of the structure and function of CtsK. Structurally, HS forms a highly stable complex with CtsK and induces its dimerization. Co-crystal structures of CtsK with bound HS oligosaccharides reveal the location of the HS binding site and suggest how HS may support dimerization. Functionally, HS plays a dual role in regulating the enzymatic activity of CtsK. While it preserves the peptidase activity of CtsK by stabilizing its active conformation, it inhibits the collagenase activity of CtsK in a sulfation level-dependent manner. These opposing effects can be explained by our finding that the HS binding site is remote from the active site, which allows HS to specifically inhibit the collagenase activity without affecting the peptidase activity. At last, we show that structurally defined HS oligosaccharides effectively block osteoclast resorption of bone in vitro without inhibiting osteoclast differentiation, which suggests that HS-based oligosaccharide might be explored as a new class of selective CtsK inhibitor for many diseases involving exaggerated bone resorption. [ABSTRACT FROM AUTHOR]

Summary: Background: Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is being increasingly recognised as a painful and debilitating condition in some affected horses, that can produce pain on prehension or result in infected, fractured and loose incisors. The only known way to completely alleviate the pain and secondary infection associated in many horses affected with EOTRH is by extraction of the diseased incisors. Currently, few large‐scale clinical outcome studies have been performed. Objectives: The purpose of this study was to determine if horses that are diagnosed with clinical EOTRH experience a statistically significant improvement in the quality of their lives after surgical extraction of all incisors and to determine if owners were satisfied with the results of the surgery. Study design: A retrospective web‐based survey was sent out to owners of horses diagnosed with EOTRH who had undergone extraction of all incisors in the previous 3 years. Methods: Forty‐eight surveys were completed, and the answers examined for statistical significance. Results: Statistically significant differences were found in the horses' body condition, dropping of hay, speed of eating, general behaviour, resistance to bridling and headshaking. In addition, owners reported that horses were 'happier' after surgery and that total extraction improved quality and extended the life of their horse. Over 90% of owners would also elect to have the procedure performed on another horse in the future. Main limitations: Retrospective surveys are prone to selection, recall and misclassification bias. Conclusions: Owners were highly satisfied with the total extraction of all incisors as a treatment for horses affected by EOTRH. Survey results showed that post‐extraction horses had improved body condition and exhibited better bridling and eating behaviours which are consistent with a decrease in dental pain. Owners felt that their horse was happier and that the surgery had improved the horse's quality of life. [ABSTRACT FROM AUTHOR]

Background and Aims Pinus massoniana: Lamb. is an important conifer forestry species in south China, but soil fertility has declined over time in monoculture plantations. Knowledge about how P. massoniana uses phosphorus (P) by distributing it among five biochemical fractions and how intercropping with broadleaf Castanopsis hystrix alters that pattern may inform long-term plantation management. Methods: We studied a single P. massoniana plantation that was split in half into a monoculture and a P. massoniana / C. hystrix intercropped plantation 25 years after establishment. We measured photosynthesis and leaf concentrations of total P, P allocated to five chemical fractions and total nitrogen (N). We also measured soil N concentrations. Results: Intercropping C. hystrix with 25-year-old P. massoniana for a further 34 years had no significant impact on P. massoniana total stem volume, although intercropped P. massoniana trees were 5 m taller. Intercropping with C. hystrix increased timber biomass due to the additional C. hystrix stems. Growth of C. hystrix was likely more limited by P than that of P. massoniana in both plantations. Total P concentration and its allocation among fractions declined with increasing leaf age, but differed in the two species. Leaf P-resorption efficiency in intercropped P. massoniana was 79%, which was about 15% greater than that in P. massoniana monoculture and in the intercropped C. hystrix. The greater P-resorption efficiency in intercropped P. massoniana than in monoculture was due to greater mobilization of P from all fractions, except phospholipids. Bulk soil N concentration was 50% greater in the intercropped plantation than in monoculture. Conclusion: Adding C. hystrix to an P. massoniana plantation was effective at increasing wood yield without compromising productivity of P. massoniana. [ABSTRACT FROM AUTHOR]

Purpose: We performed a prospective one-year multi-imaging study to assess the clinical outcomes and rate of disc resorption in acute lumbar disc herniation (LDH) patients undergoing inflammation-preserving treatment (i.e. no NSAIDS, steroids). Methods: All patients received gabapentin to relieve leg pain, 12 sessions of acupuncture. Repeat MRI was performed, every 3 months, after 12 sessions of treatment continued for those without 40% reduction in herniated disc sagittal area. Disc herniations sizes were measured on sagittal T2W MRI sequences, pre-treatment and at post-treatment intervals. Patients were stratified to fast, medium, slow, and prolonged recovery groups in relation to symptom resolution and disc resorption. Results: Ninety patients (51% females; mean age: 48.6 years) were assessed. Mean size of disc herniation was 119.54 ± 54.34 mm2, and the mean VAS-Leg score was 6.12 ± 1.13 at initial presentation. A total of 19 patients (21.1%) improved at the time of the repeat MRI (i.e. within first 3 months post-treatment). 100% of all patient had LDH resorption within one year (mean: 4.4. months). There was no significant difference at baseline LDH between fast, medium, slow, and prolonged resorption groups. Initial LDH size was weakly associated with degree of leg pain at baseline and initial gabapentin levels. Surgery was avoided in all cases. Conclusion: This is the first study to note inflammation-preserving treatment, without conventional anti-inflammatory and steroid medications, as safe and effective for patients with an acute LDH. Rate of disc resorption (100%) was higher than comparative recent meta-analysis findings (66.7%) and no patient underwent surgery. [ABSTRACT FROM AUTHOR]

Resorption within cortices of long bones removes excess mass and damaged tissue and increases during periods of reduced mechanical loading. Returning to high‐intensity exercise may place bones at risk of failure due to increased porosity caused by bone resorption. We used point‐projection X‐ray microscopy images of bone slices from highly loaded (metacarpal, tibia) and minimally loaded (rib) bones from 12 racehorses, 6 that died during a period of high‐intensity exercise and 6 that had a period of intense exercise followed by at least 35 days of rest prior to death, and measured intracortical canal cross‐sectional area (Ca.Ar) and number (N.Ca) to infer remodelling activity across sites and exercise groups. Large canals that are the consequence of bone resorption (Ca.Ar >0.04 mm2) were 1.4× to 18.7× greater in number and area in the third metacarpal bone from rested than exercised animals (p = 0.005–0.008), but were similar in number and area in ribs from rested and exercised animals (p = 0.575–0.688). An intermediate relationship was present in the tibia, and when large canals and smaller canals that result from partial bony infilling (Ca.Ar >0.002 mm2) were considered together. The mechanostat may override targeted remodelling during periods of high mechanical load by enhancing bone formation, reducing resorption and suppressing turnover. Both systems may work synergistically in rest periods to remove excess and damaged tissue. [ABSTRACT FROM AUTHOR]

The main objective of this retrospective analysis was to report on the long-term clinical and radiographic outcomes (>10 years) in a series of patients who have previously undergone hemiarthroplasty for proximal humerus fracture. The charts of 11 patients (12 shoulders) who underwent hemiarthroplasty for proximal humerus fractures were retrospectively analyzed and stratified based on tuberosity healed (TH) or tuberosity resorption (TR). The primary end points included range of motion measurements and patient-reported outcome scores. We obtained forward elevation, exterx nal rotation, internal rotation, Simple Shoulder Test, American Shoulder and Elbow Surgeons scores, and Visual Analog Scale (VAS) scores. Tuberosity healing or resorption, acromiohumeral interval, subluxation, and humeral radiolucency were analyzed separately by 2 fellowship-trained orthopedic surgeons. The mean age at surgery for TH patients was 60.0 ± 9.8 years and for TR patients was 57.7 ± 4.3 years. There were 7 cases in tuberosity healing cohort and 5 cases in the tuberosity resorption cohort. Implant survivorship at final follow-up was 100% (7/7) for TH and 60% (3/5) for TR; 2 patients who failed hemiarthroplasty were converted to reverse total shoulder arthroplasty. Mean postoperative forward elevation (TH: 155°, TR: 36°; P value <.01), external rotation (TH: 59°, TR: 28°; P value <.01), and internal rotation (TH:T12, TR:L3; P value =.08) were higher in the TH cohort. American Shoulder and Elbow Surgeons scores (TH: 90, TR: 40; P value <.01) and Simple Shoulder Test scores (TH: 9, TR: 2; P value <.01) were statistically significant between the 2 cohorts while VAS scores approached significance (mean VAS [TH: 1, TR: 4; P value =.08]). To our knowledge, this study provides the longest follow-up to date for outcomes following hemiarthroplasty with fracture. Significant improvements in shoulder function and reduction in pain levels are sustainable even after 19 years in patients whose tuberosity heals. Hemiarthroplasty remains a viable option for younger candidates whose tuberosity will heal postoperatively. [ABSTRACT FROM AUTHOR]

Abstract Bioresorbable stents represent a revolutionary treatment for coronary artery disease. Such a device offers the prospect for complete naturalization of artery lumen after strut resorption and restoration of vasomotion while curtailing the duration of dual anti‐platelet therapy. The prototype bioresorbable scaffold (BRS—ABSORB GT1) demonstrated good feasibility and safety in the initial studies compared to metallic drug eluting stent but later fell out of favor due to multiple report of stent thrombosis and target lesion failure. Unpredictable resorption of struts turned out to be one of the “Achilles heel” of the BRS and stent strut were still visible in vessel on optical coherence tomography (OCT) at 3 years. We report a case of differential resorption of two ABSORB BRS implanted simultaneously in the same patient by the same operator. Follow up coronary angiogram revealed only minimal plaques on right coronary artery (RCA) and left anterior descending artery (LAD). The BRS were identified on cine‐angiogram by their radio‐opaque markers at both ends. The OCT run in LAD artery revealed “ghost remnants” of BRS struts in LAD, whereas the RCA BRS had completely healed with minimal “ghost” struts. The ghost remnants of BRS resembled the original “Check box” appearance on OCT during the index implantation.

The Notch pathway is an evolutionarily preserved signaling pathway involved in a variety of vital cell functions. Additionally, it is one of the key regulators of inflammation, and controls the differentiation and function of different cells. Moreover, it was found to be involved in skeletal development and bone remodeling process. This review provides an overview of the involvement of the Notch signaling pathway in the pathogenesis of alveolar bone resorption in different forms of pathological conditions such as apical periodontitis, periodontal disease, and peri-implantitis. In vitro and in vivo evidence have confirmed the involvement of Notch signaling in alveolar bone homeostasis. Nonetheless, Notch signaling system, along with complex network of different biomolecules are involved in pathological process of bone resorption in apical periodontitis, periodontitis, and peri-implantitis. In this regard, there is a substantial interest to control the activity of this pathway in the treatment of disorders associated with its dysregulation. This review provides knowledge on Notch signaling and outlines its functions in alveolar bone homeostasis and alveolar bone resorption. Further investigations are needed to determine whether inhibition of the Notch signaling pathways might be beneficial and safe as a novel approach in the treatment of these pathological conditions.

Background—We evaluated whether the oral intake of high-molecular-weight hyaluronic acid (HMWHA) in association with alpha lipoic acid (ALA), magnesium, vitamin B6, and vitamin D can improve the resorption of subchorionic hematoma in cases of threatened miscarriage. Methods—In this study, we enrolled 56 pregnant women with threatened miscarriage (i.e., subchorionic hematomas, pelvic pain/uterine contractions, and/or vaginal bleeding) between the 6th and the 13th week of gestation. They were treated with vaginal progesterone (200 mg/twice a day) (control group; n = 25) or vaginal progesterone plus oral 200 mg HMWHA, 100 mg ALA, 450 mg magnesium, 2.6 mg vitamin B6, and 50 mcg vitamin D (treatment group; n = 31; DAV®-HA, LoLi Pharma srl, Rome, Italy). An ultrasound scan was performed at the first visit (T0) and after 7 days (T1) and 14 days (T2) until hematoma resorption. Results—At the ultrasound scan, the treatment group showed faster resorption of the subchorionic hematoma compared with the control group, both at T1 (control group 140 (112–180), treated group 84 (40–112), p < 0.0031), and T2 (control group: 72 (48–112), treated group: 0 (0–0), p < 0.0001). Moreover, subjective symptoms, such as vaginal bleeding, abdominal pain, and uterine contractions, showed a faster decrease in the treatment group than in the control group. Conclusions—The association may more rapidly improve the resolution of threatened miscarriage and related symptoms compared to the standard local protocol. [ABSTRACT FROM AUTHOR]

Aim: To use auto‐transplantation of a central incisor and canine and repositioning of a lateral incisor with corticotomy as an alternative to complex lengthy orthodontics and possible tooth loss. Method: Following initial consultation in a joint orthodontic/oral surgery clinic in Guy's Hospital, the decision was made to carry out auto‐transplantation of the ectopic teeth under general anaesthesia. The procedure included extraction of retained primary teeth, auto‐transplantation of upper right permanent central incisor and canine, segmental osteotomy/corticotomy to reposition the lateral incisor, followed by splinting of the upper 3–3 for 6 weeks. The patient was reviewed multiple times over a 2.5‐year period and no signs of inflammation, ankylosis, sensitivity, root resorption, mobility or loss of vitality was noted. Discussion: Auto‐transplantation is an underutilised technique despite being used for over 70 years. It does, however, have its limitations and there are several factors that can affect its success and predictability. This case highlights that it can be an excellent alternative to lengthy and difficult orthodontic treatment and resulted in avoidance of loss of teeth. This treatment method reduced time and cost to the NHS as well as improved the patient journey. It is important to work closely with colleagues and adopt a multidisciplinary approach to treatment planning and have an awareness for alternative treatment options that are available for joint orthodontic/oral surgery cases. Conclusion: Auto‐transplantation, in certain cases and conditions, can be very successful and save both patient and the NHS time and money. Greater awareness of this technique is required so that it can be offered more regularly as a treatment option. [ABSTRACT FROM AUTHOR]

Bone health is controlled by the balance between bone formation by osteoblasts and degradation by osteoclasts. A disequilibrium in favor of bone resorption leads to osteolytic diseases characterized by decreased bone density. Osteoclastic resorption is dependent on the assembly of an adhesion structure: the actin ring, also called podosome belt or sealing zone, which is composed of a unique patterning of podosomes stabilized by microtubules. A better understanding of the molecular mechanisms regulating the crosstalk between actin cytoskeleton and microtubules network is key to find new treatments to inhibit bone resorption. Evidence points to the importance of the fine tuning of the activity of the small GTPase RHOA for the formation and maintenance of the actin ring, but the underlying mechanism is not known. We report here that actin ring disorganization upon microtubule depolymerization is mediated by the activation of the RHOA-ROCK signaling pathway. We next show the involvement of GEFH1, one of RHOA guanine exchange factor highly expressed in osteoclasts, which has the particularity of being negatively regulated by sequestration on microtubules. Using a CRISPR/Cas9-mediated GEF-H1 knock-down osteoclast model, we demonstrate that RHOA activation upon microtubule depolymerization is mediated by GEF-H1 release. Interestingly, although lower levels of GEF-H1 did not impact sealing zone formation in the presence of an intact microtubule network, sealing zone was smaller leading to impaired resorption. Altogether, these results suggest that a fine tuning of GEF-H1 through its association with microtubules, and consequently of RHOA activity, is essential for osteoclast sealing zone stability and resorption function. [ABSTRACT FROM AUTHOR]

Bone flap resorption is a known complication of postdecompressive autologous cranioplasty. Although several potential etiopathogenetic factors have been investigated, their role is still under discussion. To further complicate things, resorption is not an all-or-nothing event, patients frequently presenting with different degrees of flap remodeling. Focus of this paper was to describe the elaboration of a score quantifying bone resorption according to a set of clinical and radiological criteria, hopefully allowing prompt identification of patients needing resurgery before the development of adverse events. In a 10-year period, 281 autologous cranioplasties were performed at our institution following decompressive craniectomy. Pertinent clinical and radiological information was registered. A set of 3 clinical and 3 radiological parameters was established to score the degree of resorption, identified under the acronym FIS (Flap Integrity Score). Three groups of patients emerged, respectively showing no (208), partial (32), and advanced (41) resorption. An overall 14.6% incidence of advanced bone resorption was found in our series. Younger age, bone multifragmentation, higher postcranioplasty Glasgow Outcome Scale scores, <2 cm distance of medial craniectomy border from the midline, and cause leading to decompressive craniectomy were associated to a statistically significant higher risk of developing a relevant bone flap resorption. The first three variables were confirmed as risk factors in multivariate analysis. Flap Integrity Score well discriminated the 3 different groups. Autologous bone repositioning is still a valuable, low-cost, cosmetically and functionally satisfactory procedure. Nonetheless, although resorption affects a minor percentage of patients, its early identification and treatment can improve long-term results. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate autophagy in an extruded disc and to compare this activity with the activity in the remaining disc after lumbar disc herniation in the same patient. Methods: In total, 12 patients (females 4, males 8) with the extruded type of lumbar disc herniation (LDH) were surgically treated. Their mean age was 54.3 ± 15.8 years (range: 29 ~ 78 years). The mean interval from the occurrence of symptoms to the operation was 9.8 ± 9.4 weeks (range: 2 ~ 24 weeks). The extruded discs were excised, and the remaining disc material removed, to prevent recurrence of herniation. Immediately after specimen collection, all tissues were stored at −70 °C prior to analysis. Autophagy was assessed immunohistochemically and via Western blotting for Atg5, Atg7, Atg12, Atg12L1, and Beclin-1. And the relationship between autophagy and apoptosis was investigated by correlation analysis of caspase-3 with autophagy proteins. Results: The expression levels of autophagic markers were significantly increased in the extruded discs compared to the remaining discs within the same patients. The mean expression levels of Atg5, Atg7, Atg12, and Beclin-1 in extruded discs were statistically significantly higher than those in the remaining discs (P < 0.01, P < 0.001, P < 0.01, and P < 0.001 respectively). Conclusions: The autophagic pathway was more active in extruded disc material than in remaining disc material within the same patient. This may explain spontaneous resorption of the extruded disc after LDH. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does a reduction in fertility and/or systemic immune cell change occur during the early implantation period in a mouse model of adenomyosis? SUMMARY ANSWER A reduction in fertility was observed in mice with adenomyosis, coinciding with local and systemic immune changes observed during the implantation period. WHAT IS KNOWN ALREADY Adenomyosis is a pathology responsible for impaired fertility in humans, with a still unclear pathophysiology. One hypothesis is that changes in immune cells observed in adenomyosis-affected uteri may alter fertility, notably the physiological immune environment necessary for successful implantation and a healthy pregnancy. STUDY DESIGN, SIZE, DURATION Randomly selected CD-1 female neonatal pups were orally dosed by administration of tamoxifen to induce adenomyosis (TAM group), while others received solvent only (control group). From 6 weeks of life, CD-1 mice of both groups were mated to study impaired fertility and related local and/or systemic immune cell changes during the early implantation period. PARTICIPANTS/MATERIALS, SETTINGS, METHODS To evaluate fertility and pregnancy outcomes, ultrasound imaging was performed at E (embryonic day) 7.5 and E11.5 to count the number of gestational sacs and the number of resorptions in eight mice of the TAM group and 16 mice of the control group. The mice were sacrificed at E18.5, and morphometric, functional (quantitative reverse transcription PCR; RT-qPCR), and histological analyses were performed on the placentas. To identify local and/or systemic immune changes during the early implantation period, 8 mice of the TAM group and 12 mice of the control group were sacrificed at E4.5. Uterine horns and spleens were collected for flow cytometry and RT-qPCR analyses to study the immune cell populations. To investigate the profile of the cytokines secreted during the early implantation period at the systemic level, supernatants from stimulated spleen cells were analyzed by multiplex immunoassay analysis. MAIN RESULTS AND THE ROLE OF CHANCE By ultrasound imaging, we observed a lower number of implantation sites (P  < 0.005) and a higher number of resorptions (P  < 0.001) in the TAM group, leading to smaller litters (average number of fetuses per litter: 1.00 [0.00; 5.25] in the TAM group versus 12.00 [9.50; 13.75] in the control group (P  < 0.001). Histological and morphometric analyses of the placentas at E18.5 showed a higher junctional/labyrinthine area ratio in the TAM group (P  = 0.005). The expression levels of genes that play a role in vascularization and placental growth (Vegf (P  < 0.001), Plgf (P  < 0.005), Pecam (P  < 0.0001), and Igf2 (P  = 0.002)) were reduced in the TAM group. In the TAM group, the percentages of macrophages, natural killer (NK) cells, and dendritic cells (DC) were significantly decreased in the uterus around the implantation period. However, the number of M1 macrophages was increased. Both macrophages and DC had an increased activation profile (higher expression of MCHII, P  = 0.012; CD80, P  = 0.015; CCR7, P  = 0.043 for macrophages, and higher expression of CD206, P  = 0.018; CXCR4, P  = 0.010; CCR7, P  = 0.006, MCHII, P  = 0.010; and CD80, P  = 0.012 for DC). In spleen, an increase in the activation of macrophages (CCR7, P  = 0.002; MCHII, P  = 0.001; and CD80, P  = 0.034) and DC was observed in the TAM group (CCR7, P  = 0.001; MCHII, P  = 0.001; Ly6C, P  = 0.015). In the uteri and the spleen, we observed increased percentages of CD4+ T lymphocytes (P  = 0.0237 and P  = 0.0136, respectively) in the TAM group and, in the uteri, an increased number of regulatory T cells (P  = 0.036) compared with the controls. LARGE SCALE DATA Not applicable. LIMITATIONS, REASONS FOR CAUTION This study is limited by the use of an animal model and the lack of intervention. WIDER IMPLICATIONS OF THE FINDINGS These data support involvement of innate and adaptive immune cells in the implantation failure and the increased rate of resorption observed in the mouse model of adenomyosis. This substantiates the need for additional research in this domain, with the goal of addressing fertility challenges in women affected by this condition. STUDY FUNDING/COMPETING INTEREST(S) None. [ABSTRACT FROM AUTHOR]

Objective Antiepileptic drugs used in the treatment of epilepsy patients have a negative effect on bone tissue, but as far as we know, tooth root resorption has not been investigated in these patients. The aim of this study was to evaluate the prevalence of external and internal root resorption and its distribution according to resorption sites in epilepsy patients using antiepileptic drugs. Material and Method Panoramic radiographs obtained before dental treatment were evaluated. While the case group consisted of only those with epilepsy, the control group included healthy subjects. The presence/absence of external and internal resorption of all teeth (except the third molars), region of resorption (cervical, middle, and apical region of the root), age, and sex were recorded in an excel file. Independent sample t-test or MannWhitney U test according to normality of distribution and a chi-square test to compare categorical variables were used. Results The resorption in 93 (21.9%) of 424 patients (236 healthy subjects and 188 epileptic patients), the groups did not significantly differ by the presence of external and internal resorption (p = 0.089 and 0.746). It was more common in those over 30 years and males (p = 0.018 and 0.013). Conclusion We concluded that the presence of resorption in epilepsy patients was not different from healthy subjects. However, in patients with epilepsy, resorption was mostly seen in the lower molars and middle 1/3 regions. Clinicians should consider our results when treating these patients. [ABSTRACT FROM AUTHOR]

The Notch pathway is an evolutionarily preserved signaling pathway involved in a variety of vital cell functions. Additionally, it is one of the key regulators of inflammation, and controls the differentiation and function of different cells. Moreover, it was found to be involved in skeletal development and bone remodeling process. This review provides an overview of the involvement of the Notch signaling pathway in the pathogenesis of alveolar bone resorption in different forms of pathological conditions such as apical periodontitis, periodontal disease, and peri-implantitis. In vitro and in vivo evidence have confirmed the involvement of Notch signaling in alveolar bone homeostasis. Nonetheless, Notch signaling system, along with complex network of different biomolecules are involved in pathological process of bone resorption in apical periodontitis, periodontitis, and peri-implantitis. In this regard, there is a substantial interest to control the activity of this pathway in the treatment of disorders associated with its dysregulation. This review provides knowledge on Notch signaling and outlines its functions in alveolar bone homeostasis and alveolar bone resorption. Further investigations are needed to determine whether inhibition of the Notch signaling pathways might be beneficial and safe as a novel approach in the treatment of these pathological conditions. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the relationship between diabetes mellitus (DM) and the disintegration of the residual alveolar ridge. Methods and Materials: The study sample comprises 144 participants (64 diabetics and 80 controls). Each participant had their orthopantomagram (OPG) taken. Considering the mandibular foreman (MF) and the lower border of mandible in OPGs as landmarks, resorption of residual ridge (RRR) in mandible was evaluated. Results: The resorption in diabetic study participants was 36.9%, while it was 19.1% in the healthy control study participants. The RRR in the diabetic group was greater than the control group (P = 0.0039). Conclusion: The resorption of RRR was greater in diabetic patients.

Context: Edentulism is a global health burden with long-life disabilities. Dental implant procedures are frequently constrained to alveolar residual ridge resorption. The resorption is strongly correlated with an imbalance of osteoblast-osteoclast activities. Estrogen well established maintain bone homeostasis. Fenugreek (Trigonella foenum-graecum L.) is a promising drug candidate to promote estrogenic activity and resist residual ridge resorption. Aims: To evaluate the drug-likeness, pharmacokinetic, toxicity as well as molecular interaction prediction between T. foenum-graecum metabolite compounds and estrogen receptor-α (ESRα)/estrogen receptor-ß (ESRß). Methods: The drug-likeness was evaluated using Lipinski’s rule of five. A web server (PkCSM) was used to predict the pharmacokinetics and toxicity. The metabolites were retrieved from the Kanaya database. The biological activity prediction was performed using PASS Online. The ligands’ structures were downloaded from PubChem National Centre for Biotechnology Information database. Proteins were obtained from Protein Data Bank. Molecular docking prediction was carried out using PyRx software and visualized using Discovery Studio Software. Results: Quercetin, naringenin, luteolin, and kaempferol displayed the highest biological activity of estrogen agonist, anti-inflammatory, and tumor necrosis factor (TNF) expression inhibitor. Four metabolites exhibited the potential to be developed as oral drugs with good absorption in gastrointestinal, moderate tissue distribution, and safe for liver tissue. Quercetin and kaempferol showed the most negative value of binding affinity. Quercetin formed three hydrogen bonds and eight hydrophobic bonds with ESRα. Luteolin had three hydrogen bonds and five hydrophobic bonds on ESRβ. Conclusions: Metabolites present in T. foenum-graecum, like quercetin, naringenin, luteolin, and kaempferol, were potential drug candidates that could act as estrogen agonists to inhibit the dental residual ridge resorption.

Abstract Objectives After a fracture of the condyle, the fractured ramus is often shortened, which causes premature dental contact on the fractured side and a contralateral open bite. The imbalance could change the load in the temporomandibular joints (TMJs). This change could lead to remodelling of the TMJs to compensate for the imbalance in the masticatory system. The load in the non-fractured condyle is expected to increase, and the load in the fractured condyle to decrease. Materials and methods These changes cannot be measured in a clinical situation. Therefore a finite element model (FEM) of the masticatory system was used. In the FEM a fractured right condyle with shortening of the ramus was induced, which varied from 2 to 16 mm. Results Results show that, with a larger shortening of the ramus, the load in the fractured condyle decreases and the load in the non-fractured condyle increases. In the fractured condyle during closed mouth a major descent in load, hence a cut-off point, was visible between a shortening of 6 mm and 8 mm. Conclusions In conclusion, the change of load could be associated with remodelling on both condyles due to shortening of the ramus. Clinical relevance The cut-off point implies that shortening over 6 mm could present more difficulty for the body to compensate.

The increase in the frequency and intensity of drought events expected in the coming decades in Western Europe may disturb forest biogeochemical cycles and create nutrient deficiencies in trees. One possible origin of nutrient deficiency is the disturbance of the partitioning of the green leaf pool during the leaf senescence period between resorption, foliar leaching and senesced leaves. However, the effects of drought events on this partitioning and the consequences for the maintenance of tree nutrition are poorly documented. An experiment in a beech forest in Meuse (France) was conducted to assess the effect of drought events on nutrient canopy exchanges and on the partitioning of the green leaf pool during the leaf senescence period. The aim was to identify potential nutritional consequences of droughts for trees. Monitoring nutrient dynamics, including resorption, chemistry of green and senesced leaves, foliar absorption and leaching in mature beech stands from 2012 to 2019 allowed us to compare the nutrient exchanges for three nondry and three dry years (i.e., with an intense drought event during the growing season). During dry years, we observed a decrease by almost a third of the potassium (K) partitioning to resorption (i.e. resorption efficiency), thus reducing the K reserve in trees for the next growing season. This result suggests that with the increased drought frequency and intensity expected for the coming decades, there will be a risk of potassium deficiency in trees, as already observed in a rainfall exclusion experiment on the same study site. Reduced foliar leaching and higher parititioning to the senesced leaves for K and phosphorus (P) were also observed. In addition, a slight increase in nitrogen (N) resorption efficiency occurred during dry years which is more likely to improve tree nutrition. The calcium (Ca) negative resorption decreased, with no apparent consequence in our study site. Our results show that nutrient exchanges in the canopy and the partitioning of the green leaf pool can be modified by drought events, and may have consequences on tree nutrition.

Bone health is controlled by the balance between bone formation by osteoblasts and degradation by osteoclasts. A disequilibrium in favor of bone resorption leads to osteolytic diseases characterized by decreased bone density. Osteoclastic resorption is dependent on the assembly of an adhesion structure: the actin ring, also called podosome belt or sealing zone, which is composed of a unique patterning of podosomes stabilized by microtubules. A better understanding of the molecular mechanisms regulating the crosstalk between actin cytoskeleton and microtubules network is key to find new treatments to inhibit bone resorption. Evidence points to the importance of the fine tuning of the activity of the small GTPase RHOA for the formation and maintenance of the actin ring, but the underlying mechanism is not known. We report here that actin ring disorganization upon microtubule depolymerization is mediated by the activation of the RHOA-ROCK signaling pathway. We next show the involvement of GEF-H1, one of RHOA guanine exchange factor highly expressed in osteoclasts, which has the particularity of being negatively regulated by sequestration on microtubules. Using a CRISPR/Cas9-mediated GEF-H1 knock-down osteoclast model, we demonstrate that RHOA activation upon microtubule depolymerization is mediated by GEF-H1 release. Interestingly, although lower levels of GEF-H1 did not impact sealing zone formation in the presence of an intact microtubule network, sealing zone was smaller leading to impaired resorption. Altogether, these results suggest that a fine tuning of GEF-H1 through its association with microtubules, and consequently of RHOA activity, is essential for osteoclast sealing zone stability and resorption function.

The widespread application of calcium carbonate is determined by its high availability in nature and simplicity of synthesis in laboratory conditions. Moreover, calcium carbonate possesses highly attractive physicochemical properties that make it suitable for a wide range of biomedical applications. This review provides a conclusive analysis of the results on using the tunable vaterite metastability in the development of biodegradable drug delivery systems and therapeutic vehicles with a controlled and sustained release of the incorporated cargo. This manuscript highlights the nuances of vaterite recrystallization to non-porous calcite, dissolution at acidic pH, biodegradation at in vivo conditions and control over these processes. This review outlines the main benefits of vaterite instability for the controlled liberation of the encapsulated molecules for the development of biodegradable natural and synthetic polymeric materials for biomedical purposes. [ABSTRACT FROM AUTHOR]

Quantification of in vitro osteoclast cultures (e.g. cell number) often relies on manual counting methods. These approaches are labour intensive, time consuming and result in substantial inter- and intra-user variability. This study aimed to develop and validate an automated workflow to robustly quantify in vitro osteoclast cultures. Using ilastik, a machine learning-based image analysis software, images of tartrate resistant acid phosphatase-stained mouse osteoclasts cultured on dentine discs were used to train the ilastik-based algorithm. Assessment of algorithm training showed that osteoclast numbers strongly correlated between manual- and automatically quantified values (r = 0.87). Osteoclasts were consistently faithfully segmented by the model when visually compared to the original reflective light images. The ability of this method to detect changes in osteoclast number in response to different treatments was validated using zoledronate, ticagrelor, and co-culture with MCF7 breast cancer cells. Manual and automated counting methods detected a 70% reduction (p < 0.05) in osteoclast number, when cultured with 10 nM zoledronate and a dose-dependent decrease with 1–10 μM ticagrelor (p < 0.05). Co-culture with MCF7 cells increased osteoclast number by ≥ 50% irrespective of quantification method. Overall, an automated image segmentation and analysis workflow, which consistently and sensitively identified in vitro osteoclasts, was developed. Advantages of this workflow are (1) significantly reduction in user variability of endpoint measurements (93%) and analysis time (80%); (2) detection of osteoclasts cultured on different substrates from different species; and (3) easy to use and freely available to use along with tutorial resources. [ABSTRACT FROM AUTHOR]

(1) Background: Proximal humerus fractures can be a debilitating condition if not properly treated. These fracture patterns are varied and differ in every patient. Functional outcomes may be determined by the integrity of the shoulder girdle involving the rotator cuff insertion. The post-operative resorption or malreduction of the greater tuberosity (GT) is an important factor contributing to the poor functional outcome of a patient. Thus, we intend to evaluate the cause-and-effect relationship between GT complications and clinical prognosis and outcomes. (2) Methods: A single-center retrospective comparative study was performed to evaluate the functional outcomes of patients undergoing operative fixation for this injury. A total of 387 consecutive cases treated operatively from 2019–2021 were included for analysis. (3) Results: 94 cases fulfilled our criteria for analysis. A matched-group comparison of 19 patients each was performed to compare demographics, post-operative fracture characteristics and clinical outcomes. (4) Conclusions: The resorption or malreduction of the GT contributes greatly to the prognostic outcome in patients treated with open reduction and internal fixation (ORIF) surgery. In our demographic study, obesity is another contributing factor affecting the parameters of post-operative reduction in proximal humerus fractures. Appropriate surgical planning and post-operative multidisciplinary care must be taken into consideration to attain a satisfactory prognostic outcome. [ABSTRACT FROM AUTHOR]

In the canine species, early pregnancy arrest before 30–40 days of pregnancy will induce intra‐uterine embryonic or foetal resorption, with very few clinical signs. If no genital examination by ultrasound is performed at that time, it will often remain unnoticed and the bitch will be qualified as infertile. It is only when pregnancy stops at a later stage, mostly after 40 days, that clinical signs will be seen. Expulsion of aborted foetuses or placentas may be observed, although the dam frequently eats the expelled tissues. Intra‐uterine mummification may also occur. This article reviews the causes of pregnancy termination in the bitch, both at the embryonic and the foetal stages, reported in the literature. Canine brucellosis is by far the most important disease concerned in this aspect. There is an important current concern about this disease, due to the fact that several outbreaks have been observed recently in Europe, and that it is a very contagious disease; it may be an underestimated zoonosis. Other bacterial causes of pregnancy arrest are sporadic. There is, however, a growing attention towards the microbiological content of raw food diets which are more and more popular among dog breeders and may—if badly prepared—contain abortifacient bacteria such as Campylobacter jejuni or Listeria monocytogenes. The abortifacient role of endogenous vaginal bacteria and mycoplasms remains unclear and may be related to an imbalanced vaginal flora with subsequent ascending bacterial contamination of the uterus. The role of Canine Herpesvirus on abortion is controversial and probably not frequent. Other viruses have been shown experimentally to induce abortion but their natural occurrence in this respect remains unknown. The same applies to the parasite Neospora caninum which is suspected, but not proven, potentially to induce pregnancy arrest in bitches. Among non‐infectious causes, uterine pathology such as cystic endometrial hyperplasia (CEH) or sub‐clinical post‐mating endometritis which can cause infertility and may also induce embryonic resorption. The role of luteal insufficiency in pregnancy arrest is probably overestimated. [ABSTRACT FROM AUTHOR]

Our understanding of the initiation and cellular mechanisms underlying endochondral resorption of Meckel's cartilage (MC) remains limited. Several studies have shown that the resorption site of MC and the mandibular incisor tooth germ are located close to each other. However, whether incisor tooth germ development is involved in MC resorption remains unclear. In this study, we aimed to elucidate the spatio‐temporal interaction between the initiation site of MC resorption and the development of incisor tooth germs in an embryonic mouse model. To this effect, we developed a histology‐based three‐dimensional (3D) reconstruction technique using paraffin‐embedded serial sections of various tissues in the jaw. The serial sections were cut in the frontal section and the tissue constituents (e.g., MC, incisor, and mineralized mandible) were studied using conventional and enzyme‐based histochemistry. The outline of each component was marked on the frontal sectional images and 3D structures were constructed. To assess the vascular architecture at the site of MC resorption, immunohistochemical staining using anti‐laminin, anti‐factor VIII, and anti‐VEGF antibodies was performed. MC resorption was first observed on the lateral incisor‐facing side of the cartilage rods at sites anterior to the mental foramen on E16.0. The 3D analysis suggested that: (a) the posterior region of the clastic cartilage resorption corresponds to the cervical loop of the incisor; (b) the cervical portion of the tooth germ inflates probably due to temporal cellular congestion prior to differentiation into matrix‐producing cells; (c) the incisor tooth germ tissue is present in close proximity to MC even in mouse with continuously growing tooth and determines the disappearance of MC as the tooth development. [ABSTRACT FROM AUTHOR]

Resorption is the active withdrawal of nutrients before leaf abscission. This mechanism represents an important strategy to maintain efficient nutrient cycling; however, resorption is poorly characterized in old-growth tropical forests growing in nutrient-poor soils. We investigated nutrient resorption from leaves in 39 tree species in two tropical forests on the Guiana Shield, French Guiana, to investigate whether resorption efficiencies varied with soil nutrient, seasonality, and species traits. The stocks of P in leaves, litter, and soil were low at both sites, indicating potential P limitation of the forests. Accordingly, mean resorption efficiencies were higher for P (35.9%) and potassium (K; 44.6%) than for nitrogen (N; 10.3%). K resorption was higher in the wet (70.2%) than in the dry (41.7%) season. P resorption increased slightly with decreasing total soil P; and N and P resorptions were positively related to their foliar concentrations. We conclude that nutrient resorption is a key plant nutrition strategy in these old-growth tropical forests, that trees with high foliar nutrient concentration reabsorb more nutrient, and that nutrients resorption in leaves, except P, are quite decoupled from nutrients in the soil. Seasonality and biochemical limitation played a role in the resorption of nutrients in leaves, but species-specific requirements obscured general tendencies at stand and ecosystem level.