Management of Serious Adverse Events Following Deoxycholic Acid Injection for Submental and Jowl Fat Reduction: A Systematic Review and Management Recommendations.

Pivotal Phase 3 randomized control trials have demonstrated a favorable safety profile for ATX-101 in submental fat (SMF) reduction; however, in real-world settings, several serious adverse events (SAEs) have been reported, most of which are procedure related and avoidable. Current understanding of the management of uncommon AEs and SAEs is based on the aesthetic surgeon's discretion, and overzealous protocols for sclerosis agents are being applied for ATX-101-induced arterial injury. This review focuses on showcasing the management of SAEs reported previously and updating it with personal clinical experiences with ATX-101 for SMF and jowl fat reduction. Along with adherence to the standard procedures for ATX-101 administration, the authors recommend investigating other potential causes of SMF accumulation and jowling mechanism, appropriate demarcation of the surface area to determine the number of vials, and assessment of the fat pad thickness to determine the number of required treatment cycles for optimal therapeutic outcomes. Surgery is preferable for jowling caused by compartment displacement (ptosis), whereas fat-reducing treatments such as ATX-101 are contraindicated for jowling caused by subcutaneous tissue atrophy. Some proactive measures that can be employed to prevent AEs include avoiding intradermal injections to prevent skin ulceration/necrosis, injecting lidocaine to check for smile asymmetry as an indication of marginal mandibular nerve proximity, administering 1 to 2 mm deeper injections in males to prevent alopecia, employing good aseptic techniques to prevent abscess formation, injecting 1 product at a time using correctly labeled syringes, and confirming the diagnosis of pyoderma gangrenosum before treating it as an infection.

Baseline assessment of microplastics in commercially important marine bivalves from New York, U.S.A.

Microplastic (MP) contamination in bivalve mollusks has become a significant concern over the last few years. These ecologically and economically valuable species are popular seafood items for human consumption. As filter feeders, bivalves may ingest MPs in their bodies, possibly impacting their physiology and fitness. Additionally, a considerable amount of the seafood that humans consume comes from coastal areas where MP concentrations tend to be the highest. This research provides the first examination of MPs in eastern oysters (Crassostrea virginica) and hard clams (Mercenaria mercenaria) that were grown locally in coastal areas of New York, contributing to a baseline for the northeast and mid-Atlantic regions of the U.S. A total of 48 eastern oysters (n = 12 per site, at four sites) and hard clams (n = 24 per site, at two sites) were sampled in summer 2021. While MP fibers and fragments (i.e. polyethylene terephthalate, polystyrene, and polypropylene) were found in some oysters, other contaminants (e.g. indigo dye, phthalocyanine, dye 823, etc.) were found in both bivalve species. Particle composition was verified using Raman microspectroscopy. Although mean MP concentrations were low in eastern oysters (i.e. 0.008 MPs g-1 of soft tissue wet weight; 0.125 MPs ind-1) and not found in hard clams, more research is needed to assess the magnitude of contamination in these edible bivalves.

Extra-mandibular Osteoradionecrosis after the Treatment of Head and Neck Cancer.

AIMS: Osteoradionecrosis (ORN) is a serious toxicity of head and neck radiotherapy. It predominantly affects the mandible. Extra-mandibular ORN is rare. The aim of this study was to report the incidence and outcomes of extra-mandibular ORNs from a large institutional database. MATERIALS AND METHODS: In total, 2303 head and neck cancer patients were treated with radical or adjuvant radiotherapy. Of these, extra-mandibular ORN developed in 13 patients (0.5%). RESULTS: Maxillary ORNs (n = 8) were a consequence of the treatment of various primaries (oropharynx = 3, sinonasal = 2, maxilla = 2, parotid = 1). The median interval from the end of radiotherapy to the development of ORN was 7.5 months (range 3-42 months). The median radiotherapy dose in the centre of the ORN was 48.5 Gy (range 22-66.5 Gy). Four patients (50%) healed in 7, 14, 20 and 41 months. All temporal bone ORNs (n = 5) developed after treatment to the parotid gland (of a total of 115 patients who received radiotherapy for parotid gland malignancy). The median interval from the end of radiotherapy to the development of ORN was 41 months (range 20-68 months). The median total dose in the centre of the ORN was 63.5 Gy (range 60.2-65.3 Gy). ORN healed in only one patient after 32 months of treatment with repeated debridement and topical betamethasone cream. CONCLUSION: Extra-mandibular ORN is a rare late toxicity and this current study provides useful information on its incidence and outcome. The risk of temporal bone ORN should be considered in the treatment of parotid malignancies and patients should be counselled. More research is required to determine the optimal management of extra-mandibular ORN, particularly on the role of the PENTOCLO regimen.

Fabrication approaches for high-throughput and biomimetic disease modeling.

There is often a tradeoff between in vitro disease modeling platforms that capture pathophysiologic complexity and those that are amenable to high-throughput fabrication and analysis. However, this divide is closing through the application of a handful of fabrication approaches-parallel fabrication, automation, and flow-driven assembly-to design sophisticated cellular and biomaterial systems. The purpose of this review is to highlight methods for the fabrication of high-throughput biomaterial-based platforms and showcase examples that demonstrate their utility over a range of throughput and complexity. We conclude with a discussion of future considerations for the continued development of higher-throughput in vitro platforms that capture the appropriate level of biological complexity for the desired application. STATEMENT OF SIGNIFICANCE: There is a pressing need for new biomedical tools to study and understand disease. These platforms should mimic the complex properties of the body while also permitting investigation of many combinations of cells, extracellular cues, and/or therapeutics in high-throughput. This review summarizes emerging strategies to fabricate biomimetic disease models that bridge the gap between complex tissue-mimicking microenvironments and high-throughput screens for personalized medicine.

Biodegradable polymeric solid implants for ultra-long-acting delivery of single or multiple antiretroviral drugs.

Lack of adherence is a key barrier to a successful human immunodeficiency virus (HIV) treatment and prevention. We report on an ultra-long-acting (ULA) biodegradable polymeric solid implant (PSI) that can accommodate one or more antiretrovirals (e.g., dolutegravir (DTG) and rilpivirine (RPV)) at translatable human doses (65% wt.) in a single implant. PSIs are fabricated using a three-step process: (a) phase inversion of a drug/polymer solution to form an initial in-situ forming solid implant, (b) micronization of dried drug-loaded solid implants, and (c) compression of the micronized drug-loaded solid powder to generate the PSI. DTG and RPV can be pre-combined in a single PLGA-based solution to make dual-drug PSI; or formulated individually in PLGA-based solutions to generate separate micronized powders and form a bilayer dual-drug PSI. Results showed that in a single or bilayer dual-drug PSI, DTG and RPV exhibited physicochemical properties similar to their pure drug analogues. PSIs were well tolerated in vivo and effectively delivered drug(s) over 180 days with concentrations above 4× PA-IC90 after a single subcutaneous administration. While biodegradable and do not require removal, these PSIs can safely be removed to terminate the treatment if required. The versatility of this technology makes it attractive as an ULA drug delivery platform for HIV and various therapeutic applications.

The current status of materials for posterior composite restorations: the advent of low shrink.

UNLABELLED: Polymerization contraction, and the stresses associated with this, have presented problems with resin composite materials, particularly when used to restore cavities in posterior teeth. This paper summarizes the problems associated with polymerization contraction and examines methods used to overcome this, in particular, by the use of materials which have reduced percentage contraction when compared with traditional materials. CLINICAL RELEVANCE: Use of a material with reduced polymerization contraction should lead to simpler restoration placement.

Ultra-long-acting tunable biodegradable and removable controlled release implants for drug delivery.

Here we report an ultra-long-acting tunable, biodegradable, and removable polymer-based delivery system that offers sustained drug delivery for up to one year for HIV treatment or prophylaxis. This robust formulation offers the ability to integrate multiple drugs in a single injection, which is particularly important to address the potential for drug resistance with monotherapy. Six antiretroviral drugs were selected based on their solubility in N-methyl-2-pyrrolidone and relevance as a combination therapy for HIV treatment or prevention. All drugs released with concentrations above their protein-adjusted inhibitory concentration and retained their physical and chemical properties within the formulation and upon release. The versatility of this formulation to integrate multiple drugs and provide sustained plasma concentrations from several weeks to up to one year, combined with its ability to be removed to terminate the treatment if necessary, makes it attractive as a drug delivery platform technology for a wide range of applications.

Minimally invasive direct restorations: a practical guide.

The primary objectives of minimum intervention dentistry (MID) are to prevent or arrest active disease using non-operative management techniques. However, patients commonly present with cavitated caries lesions or failed restorations that are in need of operative intervention. Although much of clinical practice is devoted to preventing and managing the effects of caries and subsequent failure of the tooth-restoration complex, the clinical survival of restorations is often poor and becomes significantly worse as they increase in size and complexity. Minimally invasive (MI) restorative techniques present a range of well-documented advantages over more tissue-destructive traditional restorations by minimising unnecessary tooth tissue loss, insult to the dentine-pulp complex and reducing the risk of iatrogenic damage to adjacent hard and soft tissues. They also maximise the strength of the residual tooth structure by use of optimal adhesive restorative materials designed to restore function and aesthetics with durable, long-lasting restorations that are easy for the patient to maintain. In contemporary oral healthcare practice, if patients are to give valid consent for operative interventions, minimally invasive options must be offered, and may be expected to be the first choice of fully informed patients. This paper describes concepts of MID and provides an update of the latest materials, equipment and clinical techniques that are available for the minimally invasive restoration of anterior and posterior teeth with direct restorations.

In vitro cavity and crown preparations and direct restorations: A comparison of performance at the start and end of the FD programme.

Aim To assess the performance and thereby the progress of the FDs when they carried out a number of simulated clinical exercises at the start and at the end of their FD year.Methods A standardised simulated clinical restorative dentistry training exercise was carried out by a group of 61 recently qualified dental graduates undertaking a 12 months' duration foundation training programme in England, at both the start and end of the programme. Participants completed a Class II cavity preparation and amalgam restoration, a Class IV composite resin restoration and two preparations for a porcelain-metal full crown. The completed preparations and restorations were independently assessed by an experienced consultant in restorative dentistry, using a scoring system based on previously validated criteria. The data were subjected to statistical analysis.Results There was wide variation in individual performance. Overall, there was a small but not statistically significant improvement in performance by the end of the programme. A statistically significant improvement was observed for the amalgam preparation and restoration, and, overall, for one of the five geographical sub-groups in the study. Possible reasons for the variable performance and improvement are discussed.Conclusions There was variability in the performance of the FDs. The operative performance of FDs at the commencement and end of their FD year indicated an overall moderately improved performance over the year and a statistically significant improvement in their performance with regard to amalgam restoration.

Guidelines for the selection, use, and maintenance of LED light-curing units - Part 1.

Light curing is a critical step in the restorative process when using light-activated resin-based composites, but it is frequently not given the attention it deserves. The selection of a reliable light curing unit (LCU) that meets the practitioner's needs is an important equipment purchase. Using an inappropriate LCU may seriously compromise the quality of care without the practitioner realising their mistake until years later. The importance of the subject is reflected by the rapidly increasing use of light-cured composites and the decline in the use of amalgam. Many changes have occurred in the equipment and materials available for making light-cured restorations in the last twenty years. This article is part of a two-part series that will describe those changes and recommend guidelines for the selection, use, and maintenance of light emitting diode light-curing units (LED LCUs). This paper (Part 1) discusses terminology, clinical studies, the development of LCUs in dentistry, the aims of light-curing, and the need to deliver an adequate amount of energy. The interaction between light source and material is briefly described to demonstrate the complex nature of the resin photopolymerisation process.

Guidelines for the selection, use, and maintenance of LED light-curing units - Part II.

This paper is the second in a two-part series on the topic of LED light-curing units (LCUs). This part discusses LCU selection, cross infection and decontamination, maintenance, the blue-light hazard, and some possible future developments for LCUs. The article focusses on the practical aspects of the subject from the clinician's perspective. Scientific aspects are dealt with in the cited literature.

The cellulose-binding domains from Cellulomonas fimi beta-1, 4-glucanase CenC bind nitroxide spin-labeled cellooligosaccharides in multiple orientations.

The N-terminal cellulose-binding domains CBDN1 and CBDN2 from Cellulomonas fimi cellulase CenC each adopt a jelly-roll beta-sandwich structure with a cleft into which amorphous cellulose and soluble cellooligosaccharides bind. To determine the orientation of the sugar chain within these binding clefts, the association of TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl-4-yl) spin-labeled derivatives of cellotriose and cellotetraose with isolated CBDN1 and CBDN2 was studied using heteronuclear 1H-15N NMR spectroscopy. Quantitative binding measurements indicate that the TEMPO moiety does not significantly perturb the affinity of the cellooligo-saccharide derivatives for the CBDs. The paramagnetic enhancements of the amide 1HN longitudinal (DeltaR1) and transverse (DeltaR2) relaxation rates were measured by comparing the effects of TEMPO-cellotetraose in its nitroxide (oxidized) and hydroxylamine (reduced) forms on the two CBDs. The bound spin-label affects most significantly the relaxation rates of amides located at both ends of the sugar-binding cleft of each CBD. Similar results are observed with TEMPO-cellotriose bound to CBDN1. This demonstrates that the TEMPO-labeled cellooligosaccharides, and by inference strands of amorphous cellulose, can associate with CBDN1 and CBDN2 in either orientation across their beta-sheet binding clefts. The ratio of the association constants for binding in each of these two orientations is estimated to be within a factor of five to tenfold. This finding is consistent with the approximate symmetry of the hydrogen-bonding groups on both the cellooligosaccharides and the residues forming the binding clefts of the CenC CBDs.

Fos induction following systemic kainic acid: early expression in hippocampus and later widespread expression correlated with seizure.

We determined the distribution of Fos protein expression in a model of generalised epilepsy caused by excessive neuronal excitation. Fos immunoreactivity was mapped in forebrain in unrestrained rats, previously prepared with an indwelling venous catheter, after the intravenous administration of kainic acid (10 mg/kg). We determined cerebral activation following various periods of exposure to kainic acid by using intravenous administration of pentobarbitone to prevent further activation. Within a few minutes, kainic acid caused episodes of staring, sniffing, wet dog shakes, nodding and chewing. Fos induction occurred initially and simultaneously in hippocampus, subiculum, septum and entorhinal cortex as early as 9.5 min after kainate injection. After up to 40 min of staring, sniffing, wet dog shakes, nodding and chewing, Fos induction was not further increased above levels present within the first 9.5 min. After 56 +/- 6 min a motor convulsion occurred, initially affecting the jaw, head and tail and variably extending to the forelimbs, trunk or hindlimbs. Following the convulsive event, additional Fos was expressed in hippocampus, thalamus, caudate-putamen and other subcortical structures and in the cerebral cortex. Fos induction was sometimes asymmetric in entorhinal, visual, piriform, cingulum, parietal and frontal cortices and in amygdala and dorsal endopiriform area. Electroencephalographic recordings after a few minutes exposure to kainic acid revealed an increased amplitude of fast frequencies in hippocampus which appeared to correlate with Fos induction in this structure. The findings are generally consistent with the reported distribution and slow development of kainic acid-induced seizure activity using electrophysiological and deoxyglucose methods. However, the Fos distribution suggests that (i) hippocampal, possibly dentate, activation precedes significant activation elsewhere, (ii) extensive involvement of other cerebral structures and cerebral cortex occurs simultaneously and correlates with motor seizures and (iii) brain structures can be recruited asymmetrically.

An audit of cavity and crown preparations and two direct restorations carried out by foundation dentists in the Oxford and Wessex Deaneries.

It is likely that many foundation dentists (FDs) will have completed only minimal amounts of restorative dentistry for a number of months immediately prior to commencing work as FDs. Thus this audit aimed to assess the performance of the FDs when they carried out a number of simulated clinical exercises: amalgam cavities and restoration; Class IV resin composite restorations; and full crown preparations for metal-ceramic restorations. A total of 67 FDs completed the assessments and some results did indicate a high level of concern and need for further evaluation of restorative practice.

Two year clinical evaluation of a low-shrink resin composite material in UK general dental practices.

OBJECTIVE: A novel resin composite system, Filtek Silorane (3M ESPE) with reduced polymerization shrinkage has recently been introduced. The resin contains an oxygen-containing ring molecule ('oxirane') and cures via a cationic ring-opening reaction rather than a linear chain reaction associated with conventional methacrylates and results in a volumetric shrinkage of ∼1%. The purpose of this study was to review the literature on a recently introduced resin composite material, Filtek Silorane, and evaluate the clinical outcome of restorations formed in this material. METHODS: Filtek Silorane restorations were placed where indicated in loadbearing situations in the posterior teeth of patients attending five UK dental practices. These were evaluated, after two years, using modified USPHS criteria. RESULTS: A total of 100 restorations, of mean age 25.7 months, in 64 patients, were examined, comprised of 30 Class I and 70 Class II. All restorations were found to be present and intact, there was no secondary caries. Ninety-seven per cent of the restorations were rated optimal for anatomic form, 84% were rated optimal for marginal integrity, 77% were rated optimal for marginal discoloration, 99% were rated optimal for color match, and 93%% of the restorations were rated optimal for surface quality. No restoration was awarded a "fail" grade. No staining of the restoration surfaces was recorded and no patients complained of post-operative sensitivity. SIGNIFICANCE: It is concluded that, within the limitations of the study, the two year assessment of 100 restorations placed in Filtek Silorane has indicated satisfactory clinical performance.

Professional encroachment: a comparison of the emergence of denturists in Canada and Oregon.

In 1978, supporters of denturism in Oregon succeeded in passing an initiative which allows denturists to provide dentures directly to the public. The steps which led to the referendum included three unsuccessful attempts to have the state legislature enact a law legalizing denturism. After capturing broad-based consumer support, the issue was placed on the ballot and passed by an overwhelming margin. Both the denturists and the dentists in Oregon adopted strategies similar to those used in Canada over 20 years ago when the issue was raised in a number of provinces. As was the case in Canada, the denturists prevailed. Denturists stressed the price differential and the issue of freedom of choice. Dentists stressed health and safety issues. The public perceived the dentists' campaign as negative and self-serving. This perception may have contributed to the election results. In order to avoid this tarnished image, dentists must anticipate the public's needs, and formulate strategies to meet such needs.