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The purinergic receptor P2X5 contributes to bone loss in experimental periodontitis

  • Kim, Hyunsoo;Kajikawa, Tetsuhiro;Walsh, Matthew C.;Takegahara, Noriko;Jeong, Yun Hee;Hajishengallis, George;Choi, Yongwon
    • BMB Reports
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    • v.51 no.9
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    • pp.468-473
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    • 2018
  • Purinergic receptor signaling is increasingly recognized as an important regulator of inflammation. The P2X family purinergic receptors P2X5 and P2X7 have both been implicated in bone biology, and it has been suggested recently that P2X5 may be a significant regulator of inflammatory bone loss. However, a role for P2X5 in periodontitis is unknown. The present study aimed to evaluate the functional role of P2X5 in ligature-induced periodontitis in mice. Five days after placement of ligature, analysis of alveolar bone revealed decreased bone loss in $P2rx5^{-/-}$ mice compared to $P2rx7^{-/-}$ and WT control mice. Gene expression analysis of the gingival tissue of ligated mice showed that IL1b, IL6, IL17a and Tnfsf11 expression levels were significantly reduced in $P2rx5^{-/-}$ compared to WT mice. These results suggest the P2X5 receptor may regulate bone loss related to periodontitis and it may thus be a novel therapeutic target in this oral disease.

The Impact of Perforator Number on Deep Inferior Epigastric Perforator Flap Breast Reconstruction

  • Grover, Ritwik;Nelson, Jonas A.;Fischer, John P.;Kovach, Stephen J.;Serletti, Joseph M.;Wu, Liza C.
    • Archives of Plastic Surgery
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    • v.41 no.1
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    • pp.63-70
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    • 2014
  • Background Perforator flaps minimize abdominal site morbidity during autologous breast reconstruction. The purpose of this study was to assess whether the number of perforators harvested influences the overall deep inferior epigastric perforator (DIEP) flap survival and flap-related complications. Methods A retrospective review was performed of all DIEP flaps performed at the Hospital of the University of Pennsylvania from 2006 to 2011. The outcomes assessed included flap loss and major complications. We compared flaps by the number of total perforators (1-4) and then carried out a subgroup analysis comparing flaps with one perforator to flaps with multiple perforators. Lastly, we conducted a post-hoc analysis based on body mass index (BMI) categorization. Results Three hundred thirty-three patients underwent 395 DIEP flaps. No significant differences were noted in the flap loss rate or the overall complications across perforator groups. However, the subgroup analysis revealed significantly higher rates of fat necrosis in the case of one-perforator flaps than in the case of multiple-perforator flaps (10.2% vs. 3.1%, P=0.009). The post-hoc analysis revealed a significant increase in the flap loss rate with increasing BMI (<30=2.0%, 30-34.9=3.1%, 35-39.9=3.1%, >40=42.9%, P<0.001) in the DIEP flaps, but no increase in fat necrosis. Conclusions This study demonstrates that the number of perforators does not impact the rate of flap survival. However, the rate of fat necrosis may be significantly higher in DIEP flaps based on a single perforator. Multiple perforators should be utilized if possible to decrease the risk of fat necrosis.

Developmental salivary gland depression in the ascending mandibular ramus: A cone-beam computed tomography study

  • Chen, Christine A.;Ahn, Yoonhee;Odell, Scott;Mupparapu, Mel;Graham, David Mattew
    • Imaging Science in Dentistry
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    • v.46 no.3
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    • pp.223-227
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    • 2016
  • A static, unilateral, and focal bone depression located lingually within the ascending ramus, identical to the Stafne's bone cavity of the angle of the mandible, is being reported. During development of the mandible, submandibular gland inclusion may lead to the formation of a lingual concavity, which could contain fatty tissue, blood vessels, or soft tissue. However, similar occurrences in the ascending ramus at the level of the parotid gland are extremely rare. Similar cases were previously reported in dry, excavated mandibles, and 3 cases were reported in living patients. A 52-year-old African American male patient was seen for pain in the mandibular teeth. Panoramic radiography showed an unusual concavity within the left ascending ramus. Cone-beam computed tomography confirmed this incidental finding. The patient was cleared for the extraction of non-restorable teeth and scheduled for annual follow-up.

Prospective Study of Central versus Peripheral Obesity in Total Knee Arthroplasty

  • Armstrong, John G.;Morris, Tyler R.;Sebro, Ronnie;Israelite, Craig L.;Kamath, Atul F.
    • Knee surgery & related research
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    • v.30 no.4
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    • pp.319-325
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    • 2018
  • Purpose: Body mass index (BMI) is often used to predict surgical difficulty in patients receiving total knee arthroplasty (TKA); however, BMI neglects variation in the central versus peripheral distribution of adipose tissue. We sought to examine whether anthropometric factors, rather than BMI alone, may serve as a more effective indication of surgical difficulty in TKA. Materials and Methods: We prospectively enrolled 67 patients undergoing primary TKA. Correlation coefficients were used to evaluate the associations of tourniquet time, a surrogate of surgical difficulty, with BMI, pre- and intraoperative anthropometric measurements, and radiographic knee alignment. Similarly, Knee Injury and Osteoarthritis Outcome Score (KOOS) was compared to BMI. Results: Tourniquet time was significantly associated with preoperative inferior knee circumference (p=0.025) and ankle circumference (p=0.003) as well as the intraoperative depth of incision at the quadriceps (p=0.014). BMI was not significantly associated with tourniquet time or any of the radiographic parameters or KOOS scores. Conclusions: Inferior knee circumference, ankle circumference, and depth of incision at the quadriceps (measures of peripheral obesity) are likely better predictors of surgical difficulty than BMI. Further study of alternative surgical indicators should investigate patients that may be deterred from TKA for high BMI, despite relatively low peripheral obesity.

Flrt2 is involved in fine-tuning of osteoclast multinucleation

  • Shirakawa, Jumpei;Takegahara, Noriko;Kim, Hyunsoo;Lee, Seoung Hoon;Sato, Kohji;Yamagishi, Satoru;Choi, Yongwon
    • BMB Reports
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    • v.52 no.8
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    • pp.514-519
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    • 2019
  • Osteoclasts are multinucleated giant cells derived from myeloid progenitors. Excessive bone resorption by osteoclasts can result in serious clinical outcomes for which better treatment options are needed. Here, we identified fibronectin leucine-rich transmembrane protein 2 (Flrt2), a ligand of the Unc5 receptor family for neurons, as a novel target associated with the late/maturation stage of osteoclast differentiation. Flrt2 expression is induced by stimulation with receptor activator of nuclear factor-kB ligand (RANKL). Flrt2 deficiency in osteoclasts results in reduced hyper-multinucleation, which could be restored by RNAi-mediated knockdown of Unc5b. Treatment with Netrin1, another ligand of Unc5b which negatively controls osteoclast multinucleation through down regulation of RANKL-induced Rac1 activation, showed no inhibitory effects on Flrt2-deficient cells. In addition, RANKL-induced Rac1 activation was attenuated in Flrt2-deficient cells. Taken together, these results suggest that Flrt2 regulates osteoclast multinucleation by interfering with Netrin 1-Unc5b interaction and may be a suitable therapeutic target for diseases associated with bone remodeling.

Resistance to local anesthesia in people with the Ehlers-Danlos Syndromes presenting for dental surgery

  • Schubart, Jane R.;Schaefer, Eric;Janicki, Piotr;Adhikary, Sanjib D.;Schilling, Amber;Hakim, Alan J.;Bascom, Rebecca;Francomano, Clair A.;Raj, Satish R.
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.19 no.5
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    • pp.261-270
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    • 2019
  • Background: People with the Ehlers-Danlos Syndromes (EDS), a group of heritable disorders of connective tissue, often report experiencing dental procedure pain despite local anesthetic (LA) use. Clinicians have been uncertain how to interpret this apparent LA resistance, as comparison of EDS and non-EDS patient experience is limited to anecdotal evidence and small case series. The primary goal of this hypothesis-generating study was to investigate the recalled adequacy of pain prevention with LA administered during dental procedures in a large cohort of people with and without EDS. A secondary exploratory aim asked people with EDS to recall comparative LA experiences. Methods: We administered an online survey through various social media platforms to people with EDS and their friends without EDS, asking about past dental procedures, LA exposures, and the adequacy of procedure pain prevention. Among EDS respondents who both received LA and recalled the specific LA used, we compared agent-specific pain prevention for lidocaine, procaine, bupivacaine, mepivacaine, and articaine. Results: Among the 980 EDS respondents who had undergone a dental procedure LA, 88% (n = 860) recalled inadequate pain prevention. Among 249 non EDS respondents only 33% (n = 83) recalled inadequate pain prevention (P < 0.001 compared to EDS respondents). The agent with the highest EDS-respondent reported success rate was articaine (30%), followed by bupivacaine (25%), and mepivacaine (22%). Conclusions: EDS survey respondents reported nearly three times the rate of LA non-response compared to non-EDS respondents, suggesting that LAs were less effective in preventing their pain associated with routine office dental procedures.