Constructing the brief diagnostic criteria for temporomandibular disorders (bDC/TMD) for field testing.

BACKGROUND: Despite advances in temporomandibular disorders' (TMDs) diagnosis, the diagnostic process continues to be problematic in non-specialist settings. OBJECTIVE: To complete a Delphi process to shorten the Diagnostic Criteria for TMD (DC/TMD) to a brief DC/TMD (bDC/TMD) for expedient clinical diagnosis and initial management. METHODS: An international Delphi panel was created with 23 clinicians representing major specialities, general dentistry and related fields. The process comprised a full day workshop, seven virtual meetings, six rounds of electronic discussion and finally an open consultation at a virtual international symposium. RESULTS: Within the physical axis (Axis 1), the self-report Symptom Questionnaire of the DC/TMD did not require shortening from 14 items for the bDC/TMD. The compulsory use of the TMD pain screener was removed reducing the total number of Axis 1 items by 18%. The DC/TMD Axis 1 10-section examination protocol (25 movements, up to 12 sets of bilateral palpations) was reduced to four sections in the bDC/TMD protocol involving three movements and three sets of palpations. Axis I then resulted in two groups of diagnoses: painful TMD (inclusive of secondary headache), and common joint-related TMD with functional implications. The psychosocial axis (Axis 2) was shortened to an ultra-brief 11 item assessment. CONCLUSION: The bDC/TMD represents a substantially reduced and likely expedited method to establish (grouping) diagnoses in TMDs. This may provide greater utility for settings requiring less granular diagnoses for the implementation of initial treatment, for example non-specialist general dental practice.

Lithium in breast milk transiently affects the renal electrolytic balance of infants.

BACKGROUND: The use of lithium during breast-feeding has not been comprehensively investigated in humans due to concerns about lithium toxicity. PROCEDURE: We analyzed lithium in the kidneys of nursed pups of lithium medicated mothers, using analytical spectroscopy in a novel rat model. The mothers were healthy rats administered lithium via gavage (1000 mg/day Li2 CO3 per 50 kg body weight). RESULTS: Lithium was detected in the breast milk, and in the blood of pups (0.08 mM), of lithium-exposed dams at post-natal day 18 (P18), during breast-feeding. No lithium was detected after breast-feeding, at P25 (4 days after cessation of nursing). The lithium pups blood had elevated urea nitrogen at P18 and reduced total T4 at P18 and P25, indicating a longer-term effect on the kidneys and the thyroid gland. Multivariate machine-learning analysis of spectroscopy data collected from the excised kidneys of pups showed elevated potassium in lithium-exposed animals both during- and after breast-feeding. The elevated renal potassium was associated with low nephrin expression in the kidneys measured immunohistochemically during breast-feeding. After lithium exposure is stopped, the filtration of lithium from the kidneys reverses these effects. Our study showed that breastfeeding during lithium use has an effect on the kidneys of the offspring in rats.

Lithium from breast-milk inhibits thyroid iodine uptake and hormone production, which are remedied by maternal iodine supplementation.

BACKGROUND: Lithium is especially taken as a maintenance medication for Bipolar Disorder. In women with bipolar disorder, lithium is often effective during postpartum period, but breast-feeding for medicated mothers is controversial because of harmful effects for her child. At present, the biological mechanisms of lithium are not well-understood, affecting its usage and overall health implications. PROCEDURE: We developed a rat lithium and breast-feeding model at human therapeutic levels to study the effects of lithium exposure through breast-milk on pups' thyroid function. Novel laser analytical spectroscopy, along with traditional blood and immunohistochemical tests, were applied to further investigate the mechanisms behind the thyroid dysfunction. Maternal iodine supplementation was evaluated as a therapeutic method to address the pups' thyroid dysfunction. RESULTS: Pups exposed to lithium via breastmilk, even with the dam on a sub-therapeutic level, experienced weight gain, reduced blood thyroxine (T4 ), and elevated blood urea nitrogen, indicating effects on thyroid and kidney function. We show that lithium inhibited iodine uptake by thyroid follicles, initiating a mechanism that reduced iodination of tyrosine, thyroglobulin cleavage, and thyroid hormone production. Importantly, infant thyroid function can be significantly improved by administering supplementary iodine to the medicated dam's diet during breast-feeding. CONCLUSION: These results elucidate the mechanisms of lithium in thyroid function, provide valuable information on use postpartum, and suggest a clinically applicable remedy to side-effects. The results are particularly important for patients (and their infants) who respond well to lithium and need, or choose, to breast-feed.

Hemicrania continua: Case series presenting in an orofacial pain clinic.

AIM OF INVESTIGATION: Hemicrania continua (HC) is an uncommon primary headache and little is known of the characteristics of such patients managed in an orofacial pain setting. This study provides clinical features of HC, its association with other disorders, and treatment outcomes of patients managed in the TMD and Orofacial Pain Clinic at the University of Minnesota. METHODS: A retrospective review of patient records was undertaken. Inclusion criteria were a diagnosis of HC and confirmation at follow-up. RESULTS: Six of the 1617 new patients seen between 2015 and 2017 met the selection criteria. Four patients presented with "facial pain", one with "toothache" and one with "jaw pain". All were female with mean age 55 ± 10.5 years (range = 41-69). Headache characteristics included unilateral (R:L = 1:1) pain of moderate intensity with severe exacerbations in the distribution of V1 (1/6), V1 + V2 (3/6) and V1 + V2 + V3 (2/6). Lacrimation and photophobia were the most common associated symptoms. Patient presentations were complicated by multiple medical and comorbid diagnoses. All were diagnosed with temporomandibular disorder (TMD). Indomethacin alone was sufficient for adequate headache control in 2/6 patients with several add-on medications providing sustained pain relief. CONCLUSIONS: Comorbid pain conditions can be expected in patients with HC presenting to orofacial pain clinics. Symptom presentation varies, and multimodal treatment approach is necessary for success.

Structural basis for discriminatory recognition of Plasmodium lactate dehydrogenase by a DNA aptamer.

DNA aptamers have significant potential as diagnostic and therapeutic agents, but the paucity of DNA aptamer-target structures limits understanding of their molecular binding mechanisms. Here, we report a distorted hairpin structure of a DNA aptamer in complex with an important diagnostic target for malaria: Plasmodium falciparum lactate dehydrogenase (PfLDH). Aptamers selected from a DNA library were highly specific and discriminatory for Plasmodium as opposed to human lactate dehydrogenase because of a counterselection strategy used during selection. Isothermal titration calorimetry revealed aptamer binding to PfLDH with a dissociation constant of 42 nM and 2:1 protein:aptamer molar stoichiometry. Dissociation constants derived from electrophoretic mobility shift assays and surface plasmon resonance experiments were consistent. The aptamer:protein complex crystal structure was solved at 2.1-Å resolution, revealing two aptamers bind per PfLDH tetramer. The aptamers showed a unique distorted hairpin structure in complex with PfLDH, displaying a Watson-Crick base-paired stem together with two distinct loops each with one base flipped out by specific interactions with PfLDH. Aptamer binding specificity is dictated by extensive interactions of one of the aptamer loops with a PfLDH loop that is absent in human lactate dehydrogenase. We conjugated the aptamer to gold nanoparticles and demonstrated specificity of colorimetric detection of PfLDH over human lactate dehydrogenase. This unique distorted hairpin aptamer complex provides a perspective on aptamer-mediated molecular recognition and may guide rational design of better aptamers for malaria diagnostics.

Differential Diagnoses for Persistent Pain Following Root Canal Treatment: A Study in the National Dental PBRN.

INTRODUCTION: Pain present six months following root canal treatment (RCT) may be either of odontogenic or non-odontogenic origin. This is important because treatments and prognoses are different; therefore, the aim of this study was to provide specific diagnoses of patients reporting pain six months after receiving initial orthograde RCT. METHODS: We enrolled patients from the Midwest region of an existing prospective observational study of pain after RCT. Pain at six months was defined as ≥ 1 day of pain and average pain intensity of at least 1/10 over the preceding month. An endodontist and an orofacial pain practitioner independently performed clinical evaluations, which included periapical and cone-beam computed tomograph (CT) radiographs, to determine diagnoses. RESULTS: Thirty-eight out of the 354 eligible patients in the geographic area (11%) met the pain criteria, with 19 (50%) consenting to be clinically evaluated. As the sole reason for pain, 7 patients (37%) were given odontogenic diagnoses (4 involving the RCT tooth, 3 involving an adjacent tooth). Eight patients (42%) were given non-odontogenic pain diagnoses (7 from referred temporomandibular disorder [TMD] pain, 1 from persistent dentoalveolar pain disorder [PDAP]). Two patients (11%) had both odontogenic and non-odontogenic diagnoses, while 2 (11%) no longer fit the pain criteria at the time of the clinical evaluation. CONCLUSION: Patients reporting "tooth" pain 6 months following RCT had a non-odontogenic pain diagnosis accounting for some of this pain, with TMD being the most frequent non-odontogenic diagnosis. Dentists should have the necessary knowledge to differentiate between these diagnoses to adequately manage their patients.

Web-Based Survey on Regenerative Endodontic Practices among Members of the American Association of Endodontists.

INTRODUCTION: The American Association of Endodontics (AAE) Regenerative Endodontics Committee reports here the web-based survey data of regenerative endodontic procedures performed by the AAE members from 2008 to 2019. METHODS: The web-based survey consisted of 2 questionnaires, a revascularization and a follow-up, including clinical and radiographic data at 3, 6, 12 or >12 months after treatment. Data from demographics, etiology, clinical protocols, radiographic, and clinical outcome as perceived by the clinicians were recorded. From 927 entries, 184 full cases were submitted and 126 were suitable for radiographic analysis. The data were divided into cases with 6-12 months and cases with >12 months recall time. Descriptive statistics and univariate analyses were performed. RESULTS: Predominantly patients were male (63%), average 10 years-old with anterior teeth (77.2%) due to trauma (69.6%). A wide variation in regenerative endodontic procedures protocols was reported by the AAE members. The most common clinical protocols used minimal instrumentation (75.5%), 2.5% or higher concentrations of sodium hypochlorite (83.7%), and antibiotic paste as intracanal medication (58.7%). The majority reported blood clot formation (56%) and most common coronal capping material was white mineral trioxide aggregates (50.5%). Increases in radiographic root length, and radiographic root area were proportional to the time lapsed after treatment. Overall, case outcomes were categorized by clinicians as successful (54.3%), uncertain (23.9%), and unsuccessful (3.8%). CONCLUSIONS: This web-based survey provides a valuable perspective on case selection, clinical protocols, and perceived outcomes for regenerative endodontic procedures and supports the need for future higher level evidence studies.

Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in adolescents, adults, and older adults: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania.

BACKGROUND: A panel convened by the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania conducted systematic reviews and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after simple and surgical tooth extraction(s) and for the temporary management (ie, definitive dental treatment not immediately available) of toothache associated with pulp and periapical diseases in adolescents, adults, and older adults. TYPES OF STUDIES REVIEWED: The panel conducted 4 systematic reviews to determine the effect of opioid and nonopioid analgesics, local anesthetics, corticosteroids, and topical anesthetics on acute dental pain. The panel used the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations, Assessment, Development and Evaluation Evidence-to-Decision Framework to formulate recommendations. RESULTS: The panel formulated recommendations and good practice statements using the best available evidence. There is a beneficial net balance favoring the use of nonopioid medications compared with opioid medications. In particular, nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen likely provide superior pain relief with a more favorable safety profile than opioids. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Nonopioid medications are first-line therapy for managing acute dental pain after tooth extraction(s) and the temporary management of toothache. The use of opioids should be reserved for clinical situations when the first-line therapy is insufficient to reduce pain or there is contraindication of nonsteroidal anti-inflammatory drugs. Clinicians should avoid the routine use of just-in-case prescribing of opioids and should exert extreme caution when prescribing opioids to adolescents and young adults.

Sensitivity and Specificity of MRI versus CBCT to Detect Vertical Root Fractures Using MicroCT as a Reference Standard.

INTRODUCTION: Vertical root fracture (VRF) in root-canal-treated teeth frequently results in tooth loss, partly because VRFs are difficult to diagnose and when detected the fracture is often beyond the point of preservation with surgical intervention. Nonionizing magnetic resonance imaging (MRI) has demonstrated the ability to detect small VRFs, but it is unknown how its diagnostic capabilities compare with the current imaging standard for VRF detection, cone-beam computed tomography (CBCT). This investigation aimed to compare the sensitivity and specificity between MRI and CBCT for detecting VRF, using micro-computed tomography (microCT) as a reference. METHODS: A total of 120 extracted human tooth roots were root canal treated using common techniques, and VRFs were mechanically induced in a proportion. Samples were imaged using MRI, CBCT, and microCT. Axial MRI and CBCT images were examined by 3 board-certified endodontists, who evaluated VRF status (yes/no) and gave a confidence assessment for that decision, from which a receiver operating characteristic curve was generated. Intra- and inter-rater reliability were calculated, sensitivity and specificity, and area under the curve. RESULTS: Intra-rater reliability was 0.29-0.48 for MRI and 0.30-0.44 for CBCT. Inter-rater reliability for MRI was 0.37 and for CBCT 0.49. Sensitivity was 0.66 (95% confidence interval [CI], 0.53-0.78) and 0.58 (95% CI, 0.45-0.70), and specificity 0.72 (95% CI, 0.58-0.83) and 0.87 (95% CI, 0.75-0.95) for MRI and CBCT, respectively. Area under the curve was 0.74 (95% CI, 0.65-0.83) for MRI and 0.75 (95% CI, 0.66-0.84) for CBCT. CONCLUSIONS: There was no significant difference in sensitivity or specificity between MRI and CBCT in detecting VRF, despite the early-stage development of MRI.

Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in children: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at the University of Pennsylvania.

BACKGROUND: A guideline panel convened by the American Dental Association Council on Scientific Affairs, American Dental Association Science and Research Institute, University of Pittsburgh School of Dental Medicine, and Center for Integrative Global Oral Health at the University of Pennsylvania conducted a systematic review and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after 1 or more simple and surgical tooth extractions and the temporary management of toothache (that is, when definitive dental treatment not immediately available) associated with pulp and furcation or periapical diseases in children (< 12 years). TYPES OF STUDIES REVIEWED: The authors conducted a systematic review to determine the effect of analgesics and corticosteroids in managing acute dental pain. They used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations. RESULTS: The panel formulated 7 recommendations and 5 good practice statements across conditions. There is a small beneficial net balance favoring the use of nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen compared with not providing analgesic therapy. There is no available evidence regarding the effect of corticosteroids on acute pain after surgical tooth extractions in children. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Nonopioid medications, specifically nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen alone or in combination with acetaminophen, are recommended for managing acute dental pain after 1 or more tooth extractions (that is, simple and surgical) and the temporary management of toothache in children (conditional recommendation, very low certainty). According to the US Food and Drug Administration, the use of codeine and tramadol in children for managing acute pain is contraindicated.

Expression, purification, crystallization and preliminary X-ray analysis of Plasmodium falciparum GTP:AMP phosphotransferase.

Adenylate kinases (AKs) are phosphotransferase enzymes that catalyze the interconversion of adenine nucleotides, thereby playing an important role in energy metabolism. In Plasmodium falciparum, three AK isoforms, namely PfAK1, PfAK2 and GTP:AMP phosphotransferase (PfGAK), have been identified. While PfAK1 and PfAK2 catalyse the conversion of ATP and AMP to two molecules of ADP, PfGAK exhibits a substrate preference for GTP and AMP and does not accept ATP as a substrate. PfGAK was cloned and expressed in Escherichia coli and purified using two-step chromatography. Brown hexagonal crystals of PfGAK were obtained and a preliminary diffraction analysis was performed. X-ray diffraction data for a single PfGAK crystal were processed to 2.9 Å resolution in space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 123.49, c = 180.82 Å, α = ß = 90, γ = 120°.

How beavers affect riverine aquatic macroinvertebrates: a review.

Background: As ecosystem engineers, the construction of dams by beavers alters stream habitat physically and biologically, making them a species of interest for habitat restoration. Beaver-created habitat changes affect a wide range of aquatic invertebrate species. However, despite numerous individual studies of how beavers affect aquatic macroinvertebrate assemblages, there has been no evaluation of the consensus of these effects across studies. Methodology: We collated and examined studies comparing beaver-created ponds to nearby lotic reaches to determine general trends in aquatic macroinvertebrate richness, density, biomass, and functional composition between habitats. From this evidence, we highight knowledge gaps in how beaver activity affects aquatic macroinvertebrates. Results: Overall, in the majority of studies, aquatic macroinvertebrate richness was higher in nearby lotic reaches compared to beaver-created ponds, but richness at coarser scales (gamma diversity) increased with the addition of beaver ponds due to increased habitat heterogeneity. Functional feeding group (FFG) patterns were highly context-dependent, though predator taxa were generally more abundant in beaver ponds than adjacent lotic reaches. Site-specific geomorphological changes, coupled with dam or riparian zone characteristics and resulting differences in basal food resources likely shape other FFG responses. Conclusions: We identify a lack of long-term studies at single or multiple sites and conclude that fine-scale approaches may improve our understanding of the dynamics of macroinvertebrates within the freshwater realm and beyond. Due to the context-dependent nature of each study, further systematic studies of beaver engineering effects across a wider variety of environmental conditions and wetland types will also help inform land and species management decisions, such as where to prioritize protection of beaver habitats in the face of a global freshwater biodiversity crisis, or where to restore beaver populations to deliver maximum benefit.

Minimal Detectable Width of Tooth Fractures Using Magnetic Resonance Imaging and Method to Measure.

INTRODUCTION: Vertical root fracture (VRF) in root canal-treated (RCT) teeth is a common cause of pain, bone resorption, and tooth loss. VRF is also difficult to diagnose and measure. Magnetic resonance imaging (MRI) has the potential to identify VRF due to beneficial partial volume averaging, without using ionizing radiation. This investigation aimed to describe the narrowest VRFs detectable based on MRI, using micro-computed tomography (microCT) as the reference standard and proposes a method using profile integrals to measure the widths of small VRFs. METHODS: VRFs were induced in 62 RCT tooth root samples. All samples were imaged in a phantom using MRI and reference imaging was obtained using microCT. The stacks of 3-dimensional axial MRIs were assessed by 3 board-certified endodontists. Evaluators determined the most coronal slice within the stack that was discernible as the extent of the VRF. This slice was measured on correlated microCT sections to determine the minimum VRF width (µm) detectable using a profile integral-based method to measure small fractures and negate the effects of the point spread function. RESULTS: Using profile integrals to measure VRF width was repeatable and resulted in estimates that were on average 1 µm smaller than known reference widths. Adjusted median VRF width detected using MRI was 45 µm (first quartile: 26 µm, third quartile: 64 µm). CONCLUSION: Using profile integrals is a valid way to estimate small VRF width. The MRI approach demonstrated ability to repeatedly detect VRFs as small as 26 µm.

Postoperative Pain: An Analysis on Evolution of Research in Half-Century.

INTRODUCTION: Examining the evolution of research parameters helps scientists to discover the well-developed and neglected aspects of knowledge. Pain after root canal treatment is a health problem affecting millions of patients. Research in this field has a meaningful impact on quality of lives. The aim of this study was to analyze the evolution of research on postoperative pain over the past 50 years. METHODS: Electronic searches were performed in Scopus and MEDLINE databases to identify studies on pain after nonsurgical root canal treatments/retreatments. The full texts of eligible articles were reviewed to determine the study category and to extract and analyze the methodological variables. A series of statistical analyses were performed to determine the trend of publications based on the variable of interest over time. RESULTS: Four hundred twenty-four articles were included. There was a positive trend for systematic reviews, studies with sample size <200, studies on single-visit treatment, and clinical trials on instrumentation and adjunct treatments (P < .05). There was a negative trend for the use of numeric rating scales, studies on multiple-visit treatments, clinical trials on medication/medicament, and studies on pain in maxillary incisors (P < .05). No trend was observed based on pulpal diagnosis or for studies with longer observation periods (>8 weeks) (P > .05). CONCLUSIONS: A paradigm shift is needed toward clinical studies with larger sample sizes, longer observation periods, and more focus on pulpal diagnoses associated with higher rates of postoperative pain. There is a need to view postoperative pain as an important patient-centered outcome and to develop and disseminate standard reporting guidelines for future studies.

New International Classification of Orofacial Pain: What Is in It For Endodontists?

Pain is a common symptom in endodontic conditions, but differential diagnostic procedures are often needed to exclude other pain origins. Thus, general dentists and endodontists need to be aware of alternative painful orofacial conditions and be able to identify them. The new International Classification of Orofacial Pain (ICOP) is the first comprehensive classification that uniquely deals with orofacial pain. The ICOP is a hierarchical classification modeled on the International Classification of Headache Disorders and covers pain in dentoalveolar and anatomically related tissues, muscle pain, temporomandibular joint pain, neuropathic pain affecting cranial nerves, pain resembling primary headaches, and idiopathic pain in the orofacial region. A description of each condition is given, and structured diagnostic criteria for each condition are proposed based on research data when available. This narrative review aims (1) to give an overview and brief explanation of the ICOP system, (2) to describe and give examples of how it can be of use to general dentists and endodontists with special attention to differential diagnosis of tooth pain, and (3) to highlight how endodontic research can contribute to validation and improvement of the classification. A comparison to other classification and diagnostic systems is also included.

Preoperative Factors Associated with Anesthesia Failure for Patients Undergoing Nonsurgical Root Canal Therapy: A National Dental Practice-Based Research Network Study.

INTRODUCTION: The aim of this study was to identify preoperative factors associated with local anesthesia failure. METHODS: The National Dental Practice-Based Research Network (www.NationalDentalPBRN.org) data from 534 patients who received a nonsurgical root canal treatment completed in a single appointment were included in this analysis. Three methods for defining anesthesia failure were used: definition 1, patient-reported level of numbness; definition 2, provider-reported quality of anesthesia; and definition 3, provider-reported use of supplemental anesthesia. Fifty-one preoperative factors were investigated and analyzed individually against the overall failure rate for each method, and multivariate generalized estimating equation logistic models were fit with predictors chosen using stepwise model selection to evaluate factors that may interact with each other. RESULTS: The overall anesthesia failure rates were 5%, 15%, and 30% for definitions 1, 2, and 3, respectively. Provider experience, diabetes, absence of sharp or aching pain, absence of smoking, and a fair expected outcome were associated with anesthesia failure (definition 1). Provider level of training, absence of a sinus tract, bite sensitivity, and stress making the pain worse were associated with anesthesia failure (definition 2). Provider level of training, pain provoked by stimulus, mandibular teeth, teeth with vital pulps, and pain interfering with daily activities were associated with the use of supplemental anesthesia (definition 3). CONCLUSIONS: With the range of 5%-30% of anesthesia failures, a few common factors across the models assessed were elucidated. Providers with higher levels of training had significantly fewer anesthesia failures. Patient self-reported history of diabetes and preoperative pain-related interference with daily activities were associated with more anesthesia failures. Greater severity of various tooth-related pain characteristics, as a group but not individually, accounted for more anesthesia failures.

Laser induced breakdown spectroscopy with machine learning reveals lithium-induced electrolyte imbalance in the kidneys.

Lithium is a major psychiatric medication, especially as long-term maintenance medication for Bipolar Disorder. Despite its effectiveness, lithium has side-effects, such as on renal function. In this study, lithium was administered to adult rats. This animal model of renal function was validated by measuring blood lithium, urea nitrogen (BUN), and thyroxine (T4) using inductively-coupled plasma mass spectrometry and enzyme-linked immunosorbent assay. The kidneys were analyzed by laser induced breakdown spectroscopy (LIBS) with 1064 nm ablation and 300-900 nm detection. Principal components analysis (PCA), radial visualization, and random forest classification were performed on the LIBS spectra for multi-element prediction and classification. Lithium at 0.34 mmol/L was detected in the blood of lithium treated subjects only. BUN was increased (6.6 vs. 5.3 mmol/L) and T4 decreased (58.12 vs. 51.4 mmol/L) in the blood of lithium subjects compared with controls, indicating renal abnormalities. LIBS detected lithium at 2.3 mmol/kg in the kidneys of lithium subjects only. Calcium was also observed to be reduced in lithium subjects, compared with controls. Subsequent PCA observed a change in the balance of sodium and potassium in the kidneys. These are key electrolytes in the body. Importantly, partial least squares regression showed that standard clinical measurements, such as the blood tests, can be used to predict kidney electrolyte measurements, which typically cannot be performed in humans. Overall, lithium accumulates in the kidneys and adversely affects renal function. The effects are likely related to electrolyte imbalance. LIBS with machine learning analysis has potential to improve clinical management of renal side-effects in patients on lithium medication.

Interexaminer Agreement in the Radiologic Identification of Apical Periodontitis/Rarefying Osteitis in the National Dental Practice-Based Research Network PREDICT Endodontic Study.

INTRODUCTION: Periapical images are routinely made in endodontics to support diagnosis and treatment decisions, but conventional imaging may not readily demonstrate inflammatory changes. This study aims to quantify disagreement in the radiologic interpretation of apical periodontitis/rarefying osteitis between 2 expert examiners and to determine if differences exist based on anatomic location. METHODS: We used 1717 pretreatment periapical images made before orthograde endodontic treatment as part of the Predicting Outcomes of Root Canal Treatment (PREDICT) study conducted within the National Dental Practice-Based Research Network. Periapical changes were assessed independently by 2 board-certified specialists, an oral and maxillofacial radiologist and an endodontist, blinded to other clinical information. If the examiners disagreed about whether a diagnosis of apical periodontitis/rarefying osteitis was justified, an adjudication was made by a third examiner. RESULTS: The overall prevalence of this radiologic diagnosis in the periapical images was 55%, and interexaminer agreement measured with the Cohen kappa statistic was calculated to be 0.56 (95% confidence interval, 0.52-0.60). Diagnostic disagreements between the 2 examiners occurred for 377 teeth (22%), with disagreements more frequent for jaw location (P = .038) and tooth type (P = .021). Differences between root number (P = .058) and jaw location and tooth groups (P = .069) were found not to be statistically significant. CONCLUSIONS: The variability of diagnostic disagreements across anatomic location and tooth type may reflect the inability of periapical images to reveal bone changes masked by the complexity and density of overlying anatomic structures, a limitation that could potentially be overcome with the use of 3-dimensional imaging.

3-year Outcome of Patients with Persistent Pain after Root Canal Treatment: The National Dental Practice-Based Research Network.

INTRODUCTION: We measured the long-term outcomes of patients reporting persistent pain 6 months after root canal treatment (RCT) and assessed the characteristics differing patients with pain chronification from those with pain resolution. METHODS: Forty-five patients previously found to have persistent pain 6 months post-RCT from the National Dental Practice-Based Research Network were approached for a 3-year follow-up, and 27 participated in the survey. The frequency of self-reported pain, its impact on the ability to perform daily activities, and health care use were measured. The differences between patients whose persistent pain continued and those whose pain resolved were assessed. RESULTS: Five patients met criteria for pain at 3.4 years (range, 3.1-3.9 years) post-RCT, which was moderate in intensity, occurred for about 3 days in the preceding month, and kept 1 patient from usual activities. Additional health care was received by 4 of 5 patients whose pain continued compared with 7 of 22 patients whose pain resolved. A longer duration of preoperative pain and higher pain intensity and interference at 6 months were found among patients with pain chronification. Of 13 patients with specific diagnoses for the persistent pain derived at 65 ± 41 days (∼8 months) post-RCT, 10 improved regardless of the diagnosis or treatment, and 11 had a temporomandibular disorder and/or headache as comorbid diagnoses (6) or causes (6) of the persistent "tooth" pain. CONCLUSIONS: Progression of persistent post-RCT pain occurred in 19% of patients. The majority (56%) of patients improved without additional interventions. Both the group that improved and the group that continued to experience pain had a mixture of odontogenic and nonodontogenic etiologies.

Glymphatic clearance of simulated silicon dispersion in mouse brain analyzed by laser induced breakdown spectroscopy.

Silicon-based devices, such as neural probes, are increasingly used as electrodes for receiving electrical signals from neural tissue. Neural probes used chronically have been known to induce inflammation and elicit an immune response. The current study detects and evaluates silicon dispersion from a concentrated source in the mouse brain using laser induced breakdown spectroscopy. Element lines for Si (I) were found at the injection site at approximately 288 nm at 3hr post-implantation, even with tissue perfusion, indicating possible infusion into neural tissue. At 24hr and 1-week post-implantation, no silicon lines were found, indicating clearance. An isolated immune response was found by CD68 macrophage response at 24hr post injection. Future studies should measure chronic silicon exposure to determine if the inflammatory response is proportional to silicon administration. The present type of protocol, coupling laser induced breakdown spectroscopy, neuroimaging, histology, immunohistochemistry, and determination of clearance could be used to investigate the glymphatic system and different tissue states such as in disease (e.g. Alzheimer's).