Evidence for the use of ultrasound therapy for the management of mandibular osteoradionecrosis

Introduction: The treatment of mandibular osteoradionecrosis includes antibiotics and curettage, hyperbaric oxygen, surgery, and more recently, therapeutic ultrasound. The aim of this thesis was to establish the possible mechanisms of action of therapeutic ultrasound, that could explain its excellent clinical results. Material and Methods: Two ultrasound machines were evaluated, a 'traditional' (1 MHz and 3 MHz) and a 'long wave' machine (45 kHz). Ultrasound was applied to human mandibular osteoblasts, gingival fibroblasts, peripheral blood monocytes (PBMc) and mice calvaria. The following in vitro assays were performed: cell proliferation, collagen and non-collagenous protein (NCP) synthesis, bone resorption, cytokines and angiogenesis factors production using ELISA and RT-PCR techniques, and nitric oxide production. To evaluate the effects of ultrasound on angiogenesis in vivo, the chick chorioallanlbic membrane assay (CAM) was used. The use of near infrared spectroscopy (NIRS) for the measurement of radiotherapy effects in the mandible (deoxyhaemoglobin concentrations) was also evaluated. Results: Ultrasound stimulated bone formation in the mice calvaria. Cell proliferation assays showed an increase of DNA synthesis in fibroblasts and osteoblasts, up to 52%. Collagen/NCR synthesis was also enhanced, in fibroblasts up to 48%, and in osteoblasts up to 112%. Bone resorption, part of the bone turnover process, was promoted, and there is suggestion that the cyclo-oxygenase pathway is involved. In relation to cytokine production, a slight stimulation of IL-1beta was noted in all cell types. There was no difference in IL-6 and TNFalpha levels. The angiogenesis factors, IL-8 and bFGF, were significantly stimulated in osteoblasts, and VEGF was significantly stimulated in fibroblasts, osteoblasts and PBMc. RT-PCR showed that ultrasound induces mRNA transcription for several cytokines and bone related proteins, with the most evident effect being the induction of VEGF transcription in osteoblasts. The CAM assay showed that direct ultrasound application and insonated medium from fibroblasts induced angiogenesis in vivo. The best overall stimulatory intensities were 15 and 30 mW/cm2(SA) with 45 kHz ultrasound, and 0.1 and 0.4 W/cm2(SAPA) with 1 MHz ultrasound. The NIRS evaluation showed that it is very sensitive to measure deoxyhaemoglobin concentrations, however these measurements are not reproducible. No age correlations could be performed, and the differences between normal and radiotherapy mandibles was not significant because of the great variability in the measurements. Conclusions: These results show that ultrasound can correct hypocellularity, hypoxia and hypovascularity observed in osteoradionecrosis. It stimulates cell proliferation, bone formation, healing, and angiogenesis. Further in vivo experiments are recommended as well as prospective clinical trials using therapeutic ultrasound for the treatment and prevention of osteoradionecrosis, but NIRS cannot be used to measure the outcome of treatment. Therapeutic ultrasound is a viable option for the management of mandibular osteoradionecrosis, since it is effective, inexpensive and readily available

COVID-19-related challenges in dental education: experiences from Australia, Brazil, and the USA

Aim: To describe the management of dental education in three dental schools during the COVID-19 crisis. Methods: Adopted strategies in the Federal University of Paraíba (UFPB), Brazil, University of Pittsburgh (UP), USA, and Griffith University (GU), Australia were detailed. Results: In the UFPB, all on-site teaching was suspended, and resources for distance learning set up as a supplementary semester to be available as face to face classes later. A protocol for clinical care followed safety measures recommended by Brazilian official health institutions. The adequacy of the physical structure, human resources, and personal protective equipment (PPE) acquisition for the return to clinical activities are currently under discussion. In the UP, learning activities were shifted to virtual teaching using lecture recordings and live sections. All elective patients care was postponed. Urgent dental cases were discussed via teledentistry. The physical layout of the dental clinics and pre-clinical laboratories were changed, allowing a safe distance between students. In the GU, all clinical and pre-clinical activities were cancelled, and theoretical activities were maintained online for all students. Several clinically based scenarios where created and delivered in the format of online problem-based learning. The reception area was redesigned, ensuring social distancing. Safety measures follow the Australia Dental Association. Conclusions: Dealing with dental education depends on the stage of the epidemic and the characteristics of each country

A systematic review on neutrophils interactions with titanium and zirconia surfaces: Evidence from in vitro studies

Objectives: This systematic review aimed to assess in vitro studies that evaluated neutrophil interactions with different roughness levels in titanium and zirconia implant surfaces. Material and Methods: An electronic search for literature was conducted on PubMed, Embase, Scopus, and Web of Science and a total of 14 studies were included. Neutrophil responses were assessed based on adhesion, cell number, surface coverage, cell structure, cytokine secretion, reactive oxygen species (ROS) production, neutrophil activation, receptor expression, and neutrophil extracellular traps (NETs) release. The method of assessing the risk of bias was done using the toxicological data reliability assessment tool (TOXRTOOL). Results: Ten studies have identified a significant increase in neutrophil functions, such as surface coverage, cell adhesion, ROS production, and NETs released when interacting with rough titanium surfaces. Moreover, neutrophil interaction with rough–hydrophilic surfaces seems to produce less proinflammatory cytokines and ROS when compared to naive smooth and rough titanium surfaces. Regarding membrane receptor expression, two studies have reported that the FcγIII receptor (CD16) is responsible for initial neutrophil adhesion to hydrophilic titanium surfaces. Only one study compared neutrophil interaction with titanium alloy and zirconia toughened alumina surfaces and reported no significant differences in neutrophil cell count, activation, receptor expression, and death. Conclusions: There are not enough studies to conclude neutrophil interactions with titanium and zirconia surfaces. However, different topographic modifications such as roughness and hydrophilicity might influence neutrophil interactions with titanium implant surfaces

Advanced osteosarcoma of the maxilla : a case report

Osteosarcomas are primary malignant bone tumours in which mesenchymal cells produce osteoid. It is generally the most common malignant bone neoplasm, although lesions of the jaw are uncommon. Osteosarcoma of the jaw (JOS) presents a lower incidence of metastasis and a better prognosis than osteosarcoma of the long bones. However, patients with JOS can exhibit advanced tumours, mainly when early diagnosis is not performed. This article reports on a case of an advanced osteosarcoma of the maxilla. A 38-year-old woman was referred for evaluation and treatment of recurrent fibrous dysplasia of the facial bones. The patient related that she had been diagnosed with fibrous dysplasia four years earlier and, since the first diagnosis, she was submitted to four surgical interventions, all followed by recurrences. The main clinical findings were redness and swelling of the facial skin, upper lip ulceration, and hard palate swelling. Computed tomography showed a large hyperdense mass in right maxilla extending to right orbit and left maxillary sinus. An incisional biopsy was performed and microscopic examination showed areas of osteoid and chondroid formation surrounded by a cellular stroma. The diagnosis of osteosarcoma was established and the patient was recommended for oncologic treatment. Unfortunately, she died six months after the diagnosis due to uncontrollable local spread

Insights into the Substrate Specificity of Archaeal Entner-Doudoroff Aldolases:The Structures of Picrophilus torridus 2-Keto-3-deoxygluconate Aldolase and Sulfolobus solfataricus 2-Keto-3-deoxy-6-phosphogluconate Aldolase in Complex with 2-Keto-3-deoxy-6-phosphogluconate

The thermoacidophilic archaea <i>Picrophilus torridus</i> and <i>Sulfolobus solfataricus</i> catabolize glucose via a nonphosphorylative Entner–Doudoroff pathway and a branched Entner–Doudoroff pathway, respectively. Key enzymes for these Entner–Doudoroff pathways are the aldolases, 2-keto-3-deoxygluconate aldolase (KDG-aldolase) and 2-keto-3-deoxy-6-phosphogluconate aldolase [KD­(P)­G-aldolase]. KDG-aldolase from <i>P. torridus</i> (Pt-KDG-aldolase) is highly specific for the nonphosphorylated substrate, 2-keto-3-deoxygluconate (KDG), whereas KD­(P)­G-aldolase from <i>S. solfataricus</i> [Ss-KD­(P)­G-aldolase] is an enzyme that catalyzes the cleavage of both KDG and 2-keto-3-deoxy-6-phosphogluconate (KDPG), with a preference for KDPG. The structural basis for the high specificity of Pt-KDG-aldolase for KDG as compared to the more promiscuous Ss-KD­(P)­G-aldolase has not been analyzed before. In this work, we report the elucidation of the structure of Ss-KD­(P)­G-aldolase in complex with KDPG at 2.35 Å and that of KDG-aldolase from <i>P. torridus</i> at 2.50 Å resolution. By superimposition of the active sites of the two enzymes, and subsequent site-directed mutagenesis studies, a network of four amino acids, namely, Arg106, Tyr132, Arg237, and Ser241, was identified in Ss-KD­(P)­G-aldolase that interact with the negatively charged phosphate group of KDPG, thereby increasing the affinity of the enzyme for KDPG. This KDPG-binding network is absent in Pt-KDG-aldolase, which explains the low catalytic efficiency of KDPG cleavage

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

Feasibility studies for the measurement of time-like proton electromagnetic form factors from p¯ p→ μ+μ- at P ¯ ANDA at FAIR

This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, | GE| and | GM| , using the p¯ p→ μ+μ- reaction at P ¯ ANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at P ¯ ANDA , using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is p¯ p→ π+π-, due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distributions of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented

The Effects of Cooperation; A Structural Model of Siblings’ Caregiving Interactions

Hervorming Sociale Regelgevin