Highlights • We created an innovative sentence reading comprehension fMRI task for children. • Specific brain activations were found in epileptic children. • Age was the best indicator of cognitive ...skills development only in healthy children. • BECTS children may follow a distinct developmental trajectory.
Abstract Maxillary expansion treatment is a commonly used procedure by orthodontists to widen a patient's upper jaw. As this is typically performed in adolescent patients, the midpalatal suture, ...connective tissue adjoining the two maxilla halves, remains unfused. Studies that have investigated patient response to expansion treatment, generally through finite element analysis, have considered this suture to behave in a linear elastic manner or it was left vacant. The purpose of the study presented here was to develop a model that could represent the midpalatal suture's viscoelastic behavior. Quasilinear viscoelastic, modified superposition, Schapery's, and Burgers modeling approaches were all considered. Raw data from a previously published study using New Zealand White Rabbits was utilized for model parameter estimation and validation. In this study, Sentalloy® coil springs at load levels of 0.49 N (50 g), 0.98 N (100 g), and 1.96 N (200 g) were used to widen the midsagittal suture of live rabbits over a period of 6 weeks. Evaluation was based on a models ability to represent experimental data well over all three load sets. Ideally, a single set of model constants could be used to represent data over all loads tested. Upon completion of the analysis it was found that the modified superposition method was able to replicate experimental data within one standard deviation of the means using a single set of constants for all loads. Future work should focus on model improvement as well as prediction of treatment outcomes.
Intravenous delivery of oncolytic viruses often leads to tumor vascular shutdown, resulting in decreased tumor perfusion and elevated tumor hypoxia. We hypothesized that using 3TSR to normalize tumor ...vasculature prior to administration of an oncolytic Newcastle disease virus (NDV) would enhance virus delivery and trafficking of immunologic cell subsets to the tumor core, resulting in systemically enhanced immunotherapy and regression of advanced-stage epithelial ovarian cancer (EOC).
Using an orthotopic, syngeneic mouse model of advanced-stage EOC, we pretreated mice with 3TSR (4 mg/kg per day) alone or followed by combination with fusogenic NDV(F3aa) (1.0 × 10
plaque-forming units).
Treatment with 3TSR normalized tumor vasculature, enhanced blood perfusion of primary EOC tumors, and induced disease regression. Animals treated with combination therapy had the greatest reduction in primary tumor mass, ascites accumulation, and secondary lesions (50% of mice were completely devoid of peritoneal metastases). Combining 3TSR + NDV(F3aa) led to enhanced trafficking of immunologic cells into the primary tumor core.
We have shown, for the first time, that NDV, like other oncolytic viruses, is a potent mediator of acute vascular shutdown and that preventing this through vascular normalization can promote regression in a preclinical model of advanced-stage ovarian cancer. This challenges the current focus on induction of intravascular thrombosis as a requisite for successful oncolytic virotherapy.
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Bone metastases are a common cause of skeletal morbidity in patients with advanced cancer. The pattern of skeletal morbidity is complex, and the number of skeletal complications is influenced by the ...duration of survival. Because many patients with cancer die before trial completion, there is a need for survival-adjusted methods to accurately assess the effects of treatment on skeletal morbidity.
Recently, a survival-adjusted cumulative mean function model has been generated that can provide an intuitive graphic representation of skeletal morbidity throughout a study. This model was applied to the placebo-control arm of a pamidronate study in patients with malignant bone disease from breast cancer.
Analysis by bone lesion location showed that spinal metastases were associated with the highest cumulative mean incidence of skeletal-related events (SREs), followed by chest and pelvic metastases. Metastases located in the extremities were associated with an intermediate incidence of SREs, and those in the skull were associated with the lowest incidence of SREs.
Application of this model to data from the placebo arm of this trial revealed important insight into the natural history of skeletal morbidity in patients with bone metastases. Based on these observations, treatment for the prevention of SREs is warranted regardless of lesion location except for metastases on the skull.
Pediatric sleep-disordered breathing (SDB) describes a spectrum of disease ranging from snoring to upper airway resistance syndrome and obstructive sleep apnea (OSA). Anatomical features assessed ...during orthodontic exams are often associated with symptoms of SDB in children. Hence, we need to determine the prevalence of positive risk for SDB in the pediatric orthodontic population compared with a general pediatric population and understand comorbidities associated with SDB risk among orthodontic patients.
Responses from Pediatric Sleep Questionnaires were collected from 390 patients between the ages of 5 and 16 years, seeking orthodontic treatment. Prevalence of overall SDB risk, habitual snoring, and sleepiness were determined in the orthodontic population and compared with those previously reported by identical methods in the general pediatric population. Additional health history information was used to assess comorbidities associated with SDB risk in 130 of the patients.
At 10.8%, the prevalence of positive SDB risk was found to be significantly higher in the general pediatric orthodontic population than in a healthy pediatric population (5%). The prevalence of snoring and sleepiness in the orthodontic population was 13.3% and 17.9%, respectively. Among the comorbidities, nocturnal enuresis (13.6%), overweight (18.2%), and attention deficit hyperactivity disorder (31.8%) had a higher prevalence in orthodontic patients with higher SDB risk (P < 0.05).
There is a higher pediatric SDB risk prevalence in the orthodontic population compared with a healthy pediatric population. Orthodontic practitioners should make SDB screening a routine part of their clinical practice.
•The prevalence of pediatric sleep-disordered breathing (SDB) risk was 10.8% in an orthodontic population.•Pediatric SDB risk was higher in the orthodontic population than in a healthy population.•A subtype of SDB patients may only be seen at orthodontic clinics.•Nocturnal enuresis, attention deficit hyperactivity disorder, and overweight were higher in patients with high SDB risk.
The aim of this study was to evaluate skeletal and dental changes after surgically assisted rapid maxillary expansion (SARME). Clinical trials were carried out that assessed skeletal and dental ...changes through cephalograms, computer tomographs or dental casts. No other simultaneous treatment during the active expansion period was accepted. Electronic databases (Pubmed, Medline, Medline In-Process & Other Non-Indexed Citations, All Evidence-based Medicine Reviews, Embase, Web of Science and Lilacs) were searched. Abstracts which appeared to fulfil the selection criteria were selected by consensus. The original articles were then retrieved and evaluated with a methodological checklist. Their references were hand searched for possible missing articles. Only 12 articles fulfilled the selection criteria. All presented methodological flaws. An individual methodological analysis of these articles was made. Expansion was greater at the molars and diminished progressively to the anterior part of the dental arch in all the evaluation periods. Vertical and sagittal skeletal changes were nil or not clinically significant. The nasal portion of the maxillary complex showed an increase in dimensions thereby improving nasal patency. An overall dental relapse of 0.5–1
mm is reported after 1 year of orthodontic treatment. The conclusions should be considered with caution because only a secondary level of evidence was found.
This study was conducted to review the efficacy and safety of oral bisphosphonates for the treatment of bone metastases in cancer patients.
Available published clinical studies of oral ...bisphosphonates in bone metastases from 1980 to the present were identified through a MEDLINE search and from literature references. Data were reviewed for efficacy and safety, with an emphasis on double blind, placebo-controlled studies; clinically relevant endpoints; and appropriate study methodology.
Etidronate, alendronate, pamidronate, risedronate, and tiludronate currently are available in the U.S. as either intravenous and/or oral formulations. Although newer bisphosphonates are more potent, oral bioavailability remains < 1%. Oral etidronate has been found to be ineffective in patients with multiple myeloma and prostate carcinoma bone metastases. Pamidronate has been found to be effective in reducing skeletal morbidity associated with bone metastases in both multiple myeloma and breast carcinoma patients when given intravenously, but is ineffective orally in multiple myeloma patients. To the authors' knowledge, there are no double blind, placebo-controlled trials of oral pamidronate in patients with breast carcinoma and bone metastases. Several clinical trials with clodronate, a bisphosphonate that is not available in the U.S., have shown mixed results in patients with myeloma and breast carcinoma bone metastases. To the authors' knowledge, there are no published trials evaluating oral alendronate, tiludronate, or risedronate in patients with metastases to bone.
Oral bisphosphonates do not appear to be as effective as intravenous administration in reducing skeletal complications in patients with metastases to bone lesions. Low oral bioavailability is the most likely reason for this difference. Oral dosing should not be substituted for intravenous administration in the treatment of malignant osteolysis.
Abstract Objective To determine how accurate and reliable is a sample of Oral Maxillofacial Radiologists (OMFRs) in screening for adenoid hypertrophy using CBCT imaging as compared to ...Nasopharyngoscopy (NP). Study Design CBCT scans of 10 patients with distinct levels of adenoid hypertrophy were randomly selected. Fourteen board-certified OMFRs classified the levels of hypertrophy. The intraclass correlation coefficient (ICC) was used to assess accuracy by comparing their diagnosis against an NP diagnosis – the reference standard. OMFRs inter-reliability was assessed. Kappa assessed dichotomous data - healthy and unhealthy patients. Results Overall, the reliability between OMFRs was good (ICC=0.79 with CI 0.63,0.93). The “statistical mode” was very good, ICC=0.81(0.43-0.94). The accuracy of OMFRs against NP was good, ICCmean = 0.69(0.43-0.94). In average, the Kappa statistic, Kmean = 0.77(0.62-0.92) demonstrated a good agreement between the OMFRs and NP. The individualized results from each evaluator were presented and investigated according to their performance. Conclusion When compared to the reference standard, the accuracy of OMFRs to classify adenoid hypertrophy on 4-level scale was moderate to strong and improved when the adenoid hypertrophy was classified as healthy/unhealthy. The reliability of OMFR was greater than 80% assuring their consistency and reliability on screening adenoids hypertrophy via CBCT.
The consequences of xerostomia on oral health have been studied for decades; however, the actual prevalence of this disorder on the general population remains controversial. The purpose of this ...systematic review was to determine the prevalence of xerostomia in population‐based samples. Electronic databases were screened for relevant articles and reference lists of pertinent articles were also hand‐searched. Thirteen articles meeting the final inclusion criteria were identified. Based on the definition of xerostomia used in this review, only publications including a subjective diagnosis of the disorder were included. All of the self‐repotted diagnoses were achieved through a questionnaire either by mail, telephone, interview or self‐administered by the patient. There was a variation across papers regarding number and content of the questions as well as guidelines for the diagnosis of xerostomia (i.e. answer yes to one or more than one question). The prevalence of xerostomia in the selected articles ranged from 0.9% to 64.8%. The majority of these studies were performed in Scandinavia. In 9 of the articles, the studied samples were 50 years and older. None of the studies evaluated the prevalence xerostomia among individuals younger than 18 years. Based on these observations, it can be concluded that there is a need for population‐based studies on prevalence of xerostomia in regions other than Scandinavia. A standardized protocol to diagnose xerostomia needs to be developed. Patient‐perceived treatment needs and impact on quality of life should be included to have a complete picture of public health implications of the disease.
Blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have recently been Food and Drug Administration approved as predictors of intracranial ...lesions on CT after mild traumatic brain injury (mTBI). However, most cases with mTBI are CT negative, and no biomarkers are approved to assist diagnosis in these individuals. In this study, we aimed to determine the optimal combination of blood biomarkers to assist mTBI diagnosis in otherwise healthy adults younger than 50 years presenting to an emergency department within 6 hours of injury. To further understand the utility of biomarkers, we assessed how biological sex, presence or absence of loss of consciousness and/or post-traumatic amnesia (LOC/PTA), and delayed presentation affected classification performance.
Blood samples, symptom questionnaires, and cognitive tests were prospectively conducted for participants with mTBI recruited from The Alfred Hospital Level 1 Emergency & Trauma Center and uninjured controls. Follow-up testing was conducted at 7 days. Simoa quantified plasma GFAP, UCH-L1, tau, neurofilament light chain (NfL), interleukin (IL)-6, and IL-1β. Area under the receiver operating characteristic (AUC) analysis assessed classification accuracy for diagnosed mTBI, and logistic regression models identified optimal biomarker combinations.
Plasma IL-6 (AUC 0.91, 95% CI 0.86-0.96), GFAP (AUC 0.85, 95% CI 0.78-0.93), and UCH-L1 (AUC 0.79, 95% CI 0.70-0.88) best differentiated mTBI (n = 74) from controls (n = 44) acutely (<6 hours), with NfL (AUC 0.81, 95% CI 0.72-0.90) the only marker to have such utility subacutely (7 days). Biomarker performance was similar between sexes and for participants with and without LOC/PTA, with the exception at 7 days, where GFAP and IL-6 retained some utility in female participants (GFAP: AUC 0.71, 95% CI 0.55-0.88; IL-6: AUC 0.71, 95% CI 0.55-0.87) and in those with LOC/PTA (GFAP: AUC 0.73, 95% CI 0.59-0.86; IL-6: AUC 0.71, 95% CI 0.57-0.84). Acute IL-6 (
= 0.50, 95% CI 0.34-0.64) outperformed GFAP and UCH-L1 combined (
= 0.35, 95% CI 0.17-0.50), with the best acute model featuring GFAP and IL-6 (
= 0.54, 95% CI 0.34-0.68).
These findings indicate that adding IL-6 to a panel of brain-specific proteins such as GFAP and UCH-L1 might assist in the acute diagnosis of mTBI in adults younger than 50 years. Multiple markers had high classification accuracy in participants without LOC/PTA. When compared with the best-performing acute markers, subacute measures of plasma NfL resulted in minimal reduction in classification accuracy. Future studies will investigate the optimal time frame over which plasma IL-6 might assist diagnostic decisions and how extracranial trauma affects utility.
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